Physiology of the endocrine system. Changes in endocrine functions with aging Physiological changes in the endocrine system

The endocrine system is a system of endocrine glands with its complex regulation, hierarchy, complex of interconnections between organs. The endocrine system of the body as a whole maintains constancy in the internal environment, which is necessary for the normal course of physiological processes. In addition, the endocrine system, together with the nervous and immune systems, provide reproductive function, growth and development of the body, the formation, utilization and storage (“in reserve” in the form of glycogen or fatty tissue) energy. The role of signals in this system is played by hormones.
Hormones - biological active substances, possessing a strictly specific and selective action, capable of changing the level of the organism's vital activity. All hormones are divided into:
- Steroid hormones - produced from cholesterol in the adrenal cortex, in the gonads.
- Polypeptide hormones - protein hormones (insulin, prolactin, ACTH, etc.)
- Hormones derived from amino acids - adrenaline, norepinephrine, dopamine, etc.
- Hormones derived from fatty acids - prostaglandins.

According to their physiological action, hormones are divided into:
- Launchers (hormones of the pituitary gland, pineal gland, hypothalamus). Affect other endocrine glands.
- Performers - influence individual processes in tissues and organs.

The physiological action of hormones is aimed at:
1) provision humoral , i.e. carried out through the blood, regulation of biological processes;
2) maintaining the integrity and constancy of the internal environment, harmonious interaction between the cellular components of the body;
3) regulation of growth, maturation and reproduction processes.
The organ that responds to this hormone is target organ (effector). The cells of this organ are equipped with receptors.

Hormones regulate the activity of all cells in the body. They affect the acuity of thinking and physical mobility, physique and height, determine hair growth, tone of voice, sex drive and behavior. Thanks to the endocrine system, a person can adapt to strong temperature fluctuations, excess or lack of food, physical and emotional stress. The study of the physiological action of the endocrine glands made it possible to reveal the secrets of sexual function and the miracle of the birth of children, as well as to answer
the question is, why are some people tall and others short, some fat, others thin, some slow, others nimble, some strong, others weak.
In a normal state, there is a harmonious balance between the activity of the endocrine glands, the state of the nervous system and the response of the target tissues (tissues to which the effect is directed). Any violation in each of these links quickly leads to deviations from the norm. Excess or insufficient production of hormones is the cause of various diseases, accompanied by profound chemical changes in the body.
He studies the role of hormones in the vital activity of the body and the normal and pathological physiology of the endocrine glands. endocrinology .

Aging and the endocrine system

The aging process is accompanied by numerous disorders of the endocrine system. It is often difficult to determine what is the cause of these disorders - old age itself or the diseases that accompany it.

In old animals, the concentrations of most hormones are reduced. The difference between young and old organisms is even more noticeable when comparing the responses of the endocrine glands to external influences. Thus, the pituitary gland of old rats responds to the action of the hypothalamic releasing factors (liberins) by secreting less tropic hormones. By artificially replenishing the substances missing in the pituitary gland of old rats, it is possible to delay or reverse the weakening of reproductive function, the development of tumors and involution of the thymus gland (thymus).

Another reason for the weakening of endocrine regulation is age-related changes in the structure of hormones and, accordingly, their activity. So, with aging, the molecular weight changes and the activity of thyrotropin (TSH) decreases. In some cases, artificial introduction of calcium into the cell prevents a decrease in its response to hormones. Perhaps this suggests a new therapy strategy. There are also changes in the binding of calcium in the cell.

In old age, the formation of catecholamines in the sympathetic part of the autonomic nervous system increases. On the other hand, the effects transmitted by the action of catecholamines on adrenergic receptors are weakened. All this narrows the range of possible responses to extreme environmental impacts. Perhaps additional amounts of catecholamines are needed for better utilization of nutrients: by acting on adipocytes, catecholamines enhance lipolysis. Through the adrenergic receptors of the liver, they also activate glycogenolysis.

In old age, there are changes in the regulation of glucose metabolism. The number of P-cells in the pancreas decreases. In response to an increase in glucose concentration, they release less insulin into the blood. Feedback, which suppresses the release of glucose by the liver (with an increase in its concentration in the blood), acts more slowly. Insulin activity decreases, respectively, the absorption of glucose by the muscles is impaired. The result of these changes is a decrease in glucose tolerance, and sometimes the development of diabetes mellitus.
The relationship between aging and the endocrine system is described by Dielman's elevation theory.

Dielman's elevation theory

In the early 1950s, the well-known Russian gerontologist V.M. Dilman put forward and substantiated the idea of \u200b\u200bthe existence of a single regulatory mechanism that determines the patterns of age-related changes in various homeostatic (maintaining the constancy of the internal environment) systems of the body. According to Dilman's hypothesis, the main link in the mechanisms of both development (lat. Elevatio - rise, in a figurative sense - development), and subsequent aging of the body is the hypothalamus - the "conductor" of the endocrine system. Some gerontologists, including Dielman, believe that many of the changes that appear in the body as a person age is due to the body's gradual loss of the ability to maintain homeostasis through hormonal control and brain regulation. Many of the symptoms of aging appear to be due to a loss of control over hormone production, resulting in either too much or too little hormone production and regulation life processes unbalanced. Menopause, for example, is caused by the loss of the hormone estrogen produced by the ovaries. This leads to a decrease in fertility and a decrease in vaginal discharge (which can interfere with sexual intercourse), decreased muscle tone, oozing and dry skin. During the climacteric period, the amount of cholesterol and blood increases, which means that after the cessation of menstruation, women are exposed on an equal basis with men to the risk of heart disease, which is associated with the fact that cholesterol deposits block the blood supply to the heart. The main reason for aging is an age-related decrease in the sensitivity of the hypothalamus to regulatory signals from the nervous system and endocrine glands. Throughout the 1960s and 80s. with the help of experimental studies and clinical observations, it was found that it is this process that leads to age-related changes in the functions of the reproductive system and the hypothalamic-pituitary-adrenal system, which provides the necessary level of glucocorticoids produced by the adrenal cortex - "stress hormones", daily fluctuations in their concentration and increased secretion during stress, and, ultimately, to the development of a state of the so-called "hyperadaptosis". The consequence of similar age-related changes in the metabolic homeostat system, which regulates appetite and energy supply of body functions, is an increase in body fat with age, a decrease in tissue sensitivity to insulin (prediabetes) and the development of atherosclerosis.
Endocrine regulation:

An important stage in the development of the elevation theory was the establishment of the role of age-related changes that naturally occur in these three main "superhomeostats" (reproductive, adaptive and metabolic), in the formation of such phenomena that are of key importance for the lifespan of an individual, such as metabolic immunosuppression and cancrophilia, i.e. ... the formation of conditions conducive to the emergence of malignant neoplasms. Developing and deepening his concept for almost 40 years, V.M. Dilman came to the conclusion that aging (and the main diseases associated with aging) is not programmed, but is a by-product of the implementation of the genetic program of development, and therefore aging occurs with a pattern inherent in the genetic program. According to Dilman's concept, aging and related diseases is a by-product of the implementation of the genetic program of ontogenesis - the development of an organism.
The ontogenetic model of age-related pathology has opened up new approaches to the prevention of premature aging and diseases associated with
age and are the main causes of human death: heart disease, malignant neoplasms, strokes, metabolic immunosuppression, atherosclerosis, diabetes mellitus of the elderly and obesity, mental depression, autoimmune and some other diseases. From the ontogenetic model it follows that the development of diseases and natural senile changes can be slowed down if the state of homeostasis is stabilized at the level reached by the end of the organism's development. If you slow down the rate of aging , then, as V.M. Dilman, it is possible to increase the species limits of human life.

Modern ideas about the mechanisms of the geroprotective action of a calorie-restricted diet, antidiabetic biguanides, peptides of the pineal gland and melatonin, some neurotropic drugs (in particular, L-DOPA and the monoamine oxidase inhibitor deprenyl), succinic acid indicate that this approach is promising.

Unfortunately, Dielman's articles in electronic format not yet, but you can read his main work "Large biological clock".

Thus, Dielman's theory is a generalization of a group of programmed death theories. The modern version of Dielman's theory is neuroendocrine theory. One of the main age-associated disorders is the insensitivity of cells to hormonal stimuli.

Pineal gland and mechanisms of aging

Now in the scientific world has become a popular expression "Epiphysis is the sundial of the body." The most significant phenomenon for living nature on Earth is the change of day and night, light and darkness. Its rotation around its axis and at the same time around the Sun measures the days, seasons and years of our life. More and more information is accumulating about the role of the pineal gland (pineal gland) as the main pacemaker of body functions. Light inhibits the production and secretion of melatonin, and therefore its maximum level in the pineal gland and blood in humans and animals of many species is observed at night, and the minimum - in the morning and afternoon. With aging, the function of the pineal gland decreases, which is manifested primarily by a disturbance in the rhythm of melatonin secretion and a decrease in the level of its secretion (Touitou, 2001; Reiter et al., 2002).
In people in the 60-74 age group, most of the physiological parameters show a positive phase shift in the circadian rhythm (~ 1.5-2 hours) with its subsequent desynchronization in people over 75 years old (Gubin, 2001). If the pineal gland is likened to the biological clock of the body, then melatonin can be likened to a pendulum, which ensures the course of these clocks and a decrease in the amplitude of which leads to their stopping. Perhaps it would be more accurate to compare the pineal gland with a sundial, in which melatonin plays the role of a shadow from a gnomon - a rod that casts a shadow from the sun. During the day, the sun is high and the shadow is short (the level of melatonin is minimal), in the middle of the night is the peak of melatonin synthesis by the pineal gland and its secretion into the blood. At the same time, it is important that melatonin has a daily rhythm, that is, the unit of its measurement is a chronological metronome - the daily rotation of the Earth around its axis.
If the pineal gland is the sundial of the body, then, obviously, any changes in the duration of daylight hours should significantly affect its functions and, ultimately, the rate of its aging. The circadian rhythm is very important not only for the temporary organization of the physiological functions of the body, but also for the duration of its life. It has been established that with age, the neuronal activity of the suprachiasmatic nucleus decreases, while, when kept under constant lighting conditions, these disorders develop faster (Watanabe et al, 1995). Old animals are resistant to the action of clorgiline, which stimulates the biosynthesis of melatonin under conditions of round-the-clock lighting; the destruction of the suprachiasmatic nucleus of the hypothalamus has the same effect (Oxenkrug, Requintina, 1998). A number of studies have shown that the violation of photoperiods can lead to a significant decrease in the life span of animals (Pittendrigh and Minis, 1972; Pittendrigh, Daan, 1974).
M. W. Hurd and M. R. Ralph (1998) investigated the role of the circadian rhythm in the aging of the organism on golden hamsters Mesocricetus auratus with the tau pacemaker mutation. The authors received 3 groups of hamsters; having a wild type (+ / +), homozygotes tau- / tau- and heterozygotes tau - / +, and then their hybrids. Preliminary three-year observations showed that tau - / + heterozygotes had a 20% shorter lifespan than homozygotes. The lifespan of mutant heterozygotes tau - / + kept at 14 hours light, 10 hours dark, was almost 7 months shorter than in groups of homozygotes + / + or tau- / tau- (p< 0.05), однако средняя продолжительность жизни обеих гомозиготных групп была практически одинаковой. При круглосуточном содержании хомячков в условиях постоянного слабого освещения (20- 40 люкс) с 10-недельного возраста средняя продолжительность жизни гетерозигот и гомозигот была одинаковой и колебалась от 15 до 18 месяцев. Для изучения причин влияния циркадного ритма на продолжительность жизни авторы имплантировали в головной мозг старых хомячков супрахиазматические ядра от плодов хомячков различного генотипа. Было установлено, что хомячки с прижившимися имплантатами жили в среднем на 4 месяца дольше, чем интактные или ложнооперированные контрольные животные. Авторы полагают, что результаты их экспериментов свидетельствуют о том, что нарушения циркадного ритма сокращают продолжительность жизни животных, тогда как их восстановление с помощью имплантации фетального супрахиазматического ядра (спонтанного осциллятора) увеличивает ее почти на 20%. Таким же эффектом, по мнению авторов, будут обладать любые воздействия, направленные на нормализацию циркадного ритма. Интересно, что разрушение осциллятора (супрахиазматического ядра) приводит к сокращению продолжительности жизни животных (DeCoursey et al., 2000).

Melatonin and aging

Melatonin is the "hormone of the night", a pineal gland hormone that regulates circadian rhythms. The main physiological effect of melatonin is to inhibit the secretion of gonadotropins. In addition, the secretion of other tropic hormones of the anterior pituitary gland decreases, but to a lesser extent, - corticotropin, thyrotropin, somatotropin.
The secretion of melatonin is subordinated to the circadian rhythm, which, in turn, determines the rhythm of gonadotropic effects and sexual function. The synthesis and secretion of melatonin depend on illumination - an excess of light inhibits its formation, and a decrease in illumination increases the synthesis and secretion of the hormone. In humans, 70% of the daily production of melatonin is accounted for at night.

For the first time, the ability of melatonin to increase the lifespan of mice was established by W. Pierpaoli and G. J. M. Maestroni (Pierpaoli, Maestroni, 1987). In November 1985, the authors began daily administrations of melatonin in drinking water (10 mg / L) to 10 male C57BL / 6J mice. 10 control animals received 0.01% ethanol solution, which served as a solvent for melatonin. At the beginning of the experiment, the mice were 575 days old (about 19 months old), and they were all quite healthy. The animals received melatonin from 18.00 to 8.30 h. 5 months after the start of the experiment, the control animals began to lose weight, were inactive, and became bald. The introduction of melatonin protected the animals from age-related weight loss and it remained at the level of 18 months. The average lifespan of mice under the influence of melatonin increased by 20%, amounting to 931 ± 80 days versus 752 ± 81 in the control group. According to the authors' calculations, the difference is significant (p 0.05).
In 1991 W. Pierpaoli et al. (1991) presented the results of three series of experiments with chronic administration of melatonin to mice of various strains. In all experiments, melatonin was administered only at night with drinking water (10 mg / l). Melatonin was administered to 15 female mice of the C3 / He strain at 12 months of age. The control group consisted of 14 mice. Melatonin not only did not increase the lifespan of these mice, but led to an increase in the incidence of neoplasms, mainly affecting the organs of the reproductive system (lymph - or reticulosarcoma, ovarian carcinoma). Data on the average life expectancy and the frequency of neoplasms in the control and experimental groups were not provided. It should be noted that female mice of the CZN / Not line are characterized by a high incidence of spontaneous breast tumors (Storer, 1966), however, the authors do not report any information about their detection in the control or experimental groups. Mice receiving melatonin lived on average 2 months less than controls.
In the second series of experiments, melatonin was administered in the daytime or at night to female NZB (New Zealand Black) mice characterized by a high incidence of autoimmune hemolytic anemia, nephrosclerosis, and systemic or localized reticulocellular tumors of type A or B. Each group contained 10 animals, and melatonin began to be administered from the age of four months. The introduction of melatonin during the day did not affect the survival of the mice, and all of them died by the age of 20 months (in the control - by the 19th month of life). With the introduction of melatonin at night at the age of 20 months, 4 out of 10 mice of this group were alive, and 2 mice survived to 22 months of age. The last mouse lived for 2 months, that is, 4 months longer than the maximum life expectancy in the control group. The authors did not observe any differences in the causes of death in the control and experimental groups.
The third series of experiments was a repetition of the experiment with male mice of the C57BL / 6 line. This time there were 20 mice in the control group and 15 mice in the experimental group at the age of 19 months. The average life span in the control was 743 ± 84 days, and in the group receiving melatonin - 871 ± 118 days (p0.05 when calculated using Student's t test). The introduction of melatonin did not significantly affect the body weight of the mice in one direction or another when compared with the control.
Later W. Pierpaoli and W. Regelson (1994) summarized old data and presented the results of new experiments to study the effect of melatonin on the lifespan of mice of different strains. Melatonin was administered with drinking water (10 mg / L) at night (from 18.00 to 8.30). The hormone was administered to female BALB / c mice at 15 months of age. The average lifespan of the 26 control animals was 715 days, while the 12 mice receiving melatonin lived an average of 843 days, that is, 18% longer. The median was 24.8 months in the control group and 28.1 months in the experimental group, respectively, and the maximum life expectancy was 27.2 and 29.4 months, respectively. The authors did not observe any differences in body weight between the mice of both groups. In another experiment, melatonin was also administered with drinking water at night at a dose of 10 mg / l to male BALB / c mice starting at 18 months of age and killed in groups 4, 7 and 8 months after the start of exposure. After 8 months of observation, the weight of the thymus, adrenal glands, and testicles of mice treated with melatonin significantly differed from those of the same age control. Similarly, indicators such as the number of lymphocytes in the peripheral blood, zinc, testosterone and thyroid hormone levels improved. The authors believe that cyclic administration of melatonin has a positive effect on mice, maintaining a younger state of the endocrine and thymic-lymphoid organs in them. It should be noted that the number of old mice in the groups was extremely small (5-6), and the control group of 3-month-old mice included only 3 animals.
S. P. Lenz et al. (1995) injected melatonin in female NZB / W mice at a single dose of 100 μg per mouse (2-3.5 mg / kg) daily in morning hours (between 08.00 and 10.00 h) or in the evening (between 17.00 and 19.00) from eight months of age and for 9 months. Each group consisted of 15 animals. It was found that the introduction of melatonin in the morning hours is significant (p<0.001) увеличивает выживаемость мышей, тогда как вечерние инъекции таким эффектом не обладали. Так, если до 34-недельного возраста дожило только 20 % контрольных мышей, в "утренней" группе были живы 65% животных, причем 30% дожили до конца периода наблюдения (44 недели). В "вечерней" группе до 34-недельного возраста дожило практически столько же (60%) мышей, однако 37-недельный возраст пережили лишь 20% животных. Авторы отметили замедление возрастного нарастания протеинурии у мышей, которым мелатонин вводили в утренние часы. К сожалению, наблюдение за животными было прекращено до естественной гибели животных во всех группах. Число мышей в группах было весьма невелико, полная аутопсия животных не производилась.
E. Mocchegiani et al. (1998) administered melatonin in drinking water (10 g / l) at night to 50 male Balb / c mice, starting at 18 months of age. 50 mice of the other group received water supplemented with zinc sulfate (22 mg / l) and 50 served as intact controls. The mice were monitored until natural death, weighed regularly, and food intake determined. The use of melatonin and zinc significantly shifted the animal survival curves to the right and increased the maximum life span of the animals by 2 and 3 months, respectively, as compared to the intact control. Neither melatonin nor zinc affected feed intake and body weight dynamics of the animals.
A. Conti and G. J. M. Maestroni (1998) studied the effect of melatonin on the lifespan of female NOD (non-obese diabetic) mice characterized by a high incidence of insulin-dependent diabetes. One of the groups of mice (n \u003d 25) underwent epiphysectomy immediately after birth, group 2 (n \u003d 30) received melatonin subcutaneously at a dose of 4 mg / kg at 4.30 pm 5 times a week, starting from the age of 4 weeks and up to 38 th week of life. Mice of group 3 were injected subcutaneously with bovine serum (PBS) according to the same scheme, and they served as a control to group 2. Mice of group 4 (n \u003d 17) were injected with melatonin with drinking water (10 mg / l) at night 5 once a week from the 4th to the 38th week of life; The 5th group consisted of 29 intact animals. Epiphysectomized mice began to die at the age of 19 weeks, their autoimmune diabetes progressed rapidly, and by the 32nd week of life, 92% of all animals in this group had died. In the control, mice began to die from the 18th week of life; however, the slope of the survival curve was significantly lower, and by the 50th week of life, 65.5% of the control animals died out. Chronic subcutaneous administration of melatonin for 33 weeks significantly slowed the rate of disease development and decreased mortality. Only 10% of mice injected with melatonin subcutaneously did not survive until the age of 50 weeks. Interestingly, injections of bovine serum also slowed the development of diabetes, but only 32% of the mice in this group survived to 50 weeks of age. The effect of melatonin administration with drinking water was less pronounced than with its subcutaneous administration: 58.8% of mice in this group survived to the end of the observation period versus 34.5% in the control (р<0.0019). Таким образом, если эпифизэктомия ускоряла развитие диабета и укорачивала продолжительность жизни мышей линии NOD, то введение мелатонина замедляло развитие заболевания и увеличивало продолжительность жизни животных (Conti, Maestroni, 1998).
In another large study, dietary melatonin (11 ppm or 68 μg / kg bw / day) was administered to male C57BL / 6 mice starting at 18 months of age (Lipman et al., 1998). The dynamics of body weight and food consumption under the influence of melatonin did not differ significantly from that in control animals. There were also no differences in mortality in the group of control mice and mice fed with melatonin diet. Thus, 50% mortality in the control occurred at the age of 26.5 months, and with the introduction of melatonin - at 26.7 months. Mortality curves, as well as data on the maximum life span of animals in different groups, are not presented in the work. Moreover, they were killed at the age of 24 months (cohort 1) or at the age when half of all animals in the group died (age of 50% mortality), that is, 6 or 8.5 months after the start of the experiment (cohort 2). The last, 3rd cohort consisted of mice that died before the age of two or before reaching the age of 50% mortality. In the first cohort there were 20 control and melatonin-treated mice, in the second, respectively, 7 and 13 mice, and in the third, respectively, 38 and 30 animals. In these three cohorts, the frequency of the developed pathological processes was assessed separately. The authors did not find any differences in the overall frequency of pathological processes between the control group and the melatonin-treated mice. However, this conclusion, in our opinion, is not entirely correct and is refuted by the data presented in the article. So, the authors have united under one heading all pathological processes, including degenerative-atrophic, lymphoproliferative, and neoplasms. At the same time, if the frequency of lymphomas among mice in the control group and in the group receiving melatonin (3rd cohort) was the same (21.1 and 23.3%, respectively), then among those who survived to the 50% mortality rate it was 28.6 and 77.9%, respectively. It is extremely surprising that there is no mention of lymphomas in mice in cohort 1, that is, those killed at the age of 24 months, which is only 2.5-3 months less than in cohort 2, while lymphomas in those who died before this time were detected in 21-23% of cases. The article completely lacks information on neoplasms of other localizations in mice of various groups. We have to state that the work of Lipman et al. (1998) contains a number of serious methodological errors that call into question the results of the entire work and its conclusions.
In the experiments of Anisimov (Anisimov et al., 2001), 50 experimental female CBA mice, starting from the age of six months, were injected with melatonin (20 mg / L) with drinking water in courses (5 consecutive days once a month). 50 intact females served as controls. The animals were monitored until they died naturally. The mice were weighed monthly and the amount of food consumed was determined. The estrous function, muscle strength, fatigue, motor activity of the mice were examined every three months, and body temperature was measured. All animals were dissected. The detected tumors were examined histologically. It was found that long-term administration of melatonin to female CBA mice slowed down age-related changes in estrous function in them and did not have any adverse effect on their physical activity. In the course of the experiment, it was found that the body temperature of the mice of the control group did not fall, and at the 9th month of the experiment it was significantly higher than in the 6th month. On the other hand, in mice receiving melatonin, body temperature significantly decreased during the entire experiment (p< 0.001). Сходная тенденция отмечена также при измерении средней температуры отдельных фаз эстрального цикла. Однако различий между значениями температуры отдельных фаз цикла практически не было. Только у мышей подопытной группы на 3-м месяце опыта температура во время эструса была достоверно выше, чем во время метаэструса и проэструса (р < 0.05).
According to the data on the effect of melatonin on the lifespan of mice, it can be seen that the dynamics of survival did not differ in both groups until the age of 22 months, after which there was a clear decrease in mortality under the influence of melatonin. If no control mice survived by the age of two, then there were 9 mice receiving melatonin. Thus, the survival curve of the melatonin-treated mice was shifted to the right compared to the survival curve of the control mice. The average lifespan of mice in both groups did not differ significantly, while the maximum lifespan under the influence of melatonin increased by almost 2.5 months.
Thus, the use of melatonin had a definite effect on spontaneous carcinogenesis in female CBA mice.The number of mice with malignant tumors in the experimental group was significantly (20%) more than in the control group. Under the influence of melatonin, the appearance of 4 leukemias and 5 adenocarcinomas of the lungs was noted (р<0.01), отсутствовавших в контрольной группе. Показано наличие опухолей матки в подопытной группе мышей. Однако под влиянием мелатонина у мышей реже развивались аденомы легких (в 2.5 раза, р<0.001). Не наблюдалось существенного влияния мелатонина на развитие новообразований какой-либо иной локализации.
In the same article, Anisimov proposed the aging-antiaging scheme, in which melatonin also plays a role:


In experiments on SHR females, melatonin was also administered with drinking water at night in two doses (2 and 20 mg / L), 5 consecutive days monthly, starting from the age of 3 months (Anisimov et al., 2003). The use of melatonin was accompanied by a slower age-related exclusion of estrous function, a slight decrease in body weight (in a low dose), and an increase in the average life span of the last 10% of mice. Melatonin at a dose of 2 mg / L significantly inhibited the development of tumors in mice of this strain (1.9 times compared with intact controls). In this case, the most pronounced effect was manifested in relation to breast adenocarcinomas, the frequency of which decreased by 4.3 times.
Thus, the data on the effect of melatonin on the lifespan and the development of spontaneous tumors in mice of various strains are rather contradictory.
If we do not take into account the experiments of V.I. Romanenko, in which melatonin was injected in a very large dose, it turns out that when administered to mice of different strains and regardless of the time of initiation of use, melatonin increased the average lifespan in 12 experiments out of 20 and in 8 had no effect. When the animals were divided by sex, it turned out that melatonin exhibited a geroprotective effect in 4 out of 5 experiments performed on males, while in females only 8 out of 15 experiments had a positive result. In 8 out of 14 experiments in which melatonin was started at a relatively young age (up to 6 months), the result was positive, and in 6 there was no effect. It should be noted that most of the described experiments were performed on a small number of animals, which undoubtedly reduces the reliability of the results obtained in such experiments. It should be noted that in 4 series of experiments in which there were a sufficient number of animals (50 in each group), three gave a positive result, that is melatonin had a geroprotective effect.

Of course, experiments to study the role of melatonin in the aging process will continue.

Insulin is a hormone that regulates metabolism. In recent years, cardiovascular diseases have taken the first place in mortality. And they are directly related to insulin imbalances. Is developing , poetically called by scientists "the quadriga of death". According to modern concepts, the unifying basis of all manifestations of the metabolic syndrome is primary insulin resistance and concomitant systemic hyperinsulinemia (increased insulin levels in the blood). Hyperinsulinemia, on the one hand, is compensatory, that is, it is necessary to overcome insulin resistance and maintain normal glucose transport into cells; on the other, pathological, contributing to the emergence and development of metabolic, hemodynamic and organ disorders, ultimately leading to the development of type 2 diabetes mellitus, coronary artery disease and other manifestations of atherosclerosis. This has been proven by a large number of experimental and clinical studies.

Until now, all the possible causes and mechanisms of the development of insulin resistance in abdominal obesity have not been fully studied, not all components of the metabolic syndrome can be clearly linked and explained by insulin resistance. The modern understanding of the causes of the syndrome is presented by the diagram:

Insulin resistance is a decrease in the response of insulin-sensitive tissues to insulin when it is sufficiently concentrated. The study of genetic factors determining the development of insulin resistance showed its polygenic nature. In the development of insulin sensitivity disorders, mutations in the genes of the insulin receptor substrate (SIR-1), glycogen synthetase, hormone-sensitive lipase, b3-adrenergic receptors, tumor necrosis factor-a, uncoupling protein (UCP-1), as well as molecular defects of proteins that transmit insulin signals (an increase in the expression of the Rad protein and UPC-1 inhibitor of insulin receptor tyrosine kinase in muscle tissue, a decrease in membrane concentration and activity of intracellular glucose transporters GLUT-4 in muscle tissue).

An important role in the development and progression of insulin resistance and associated metabolic disorders is played by the adipose tissue of the abdominal region, neurohormonal disorders accompanying abdominal obesity, and increased activity of the sympathetic nervous system.
Hormonal disorders associated with visceral-abdominal obesity:
- increased cortisol
- increase in testosterone and androstenedione in women
- decrease in progesterone
- decrease in testosterone in men
- decrease in growth hormone
- increased insulin
- increased norepinephrine
Hormonal disorders primarily contribute to the deposition of fat mainly in the visceral region, as well as directly or indirectly the development of insulin resistance and metabolic disorders.
A complex cascade of reactions leads to the onset and development of age-related diseases and death.

The article "Metabolic Syndrome, IGF-1 and Insulin Action" by Japanese scientists from the Keio University School of Medicine discusses these issues in detail.

Insulin paradox

One of the groups of age-associated diseases - various neurodegenerative diseases have different times of manifestation, different proteins are involved in their development. Familial forms of diseases manifest in the fifth decade of life, sporadic cases - after 70 years. Until recently, the relationship between the aging process and the aggregation of toxic proteins (a common feature of neurodegenerative diseases) was unclear. The signaling pathway of insulin and insulin-like growth factor 1 (IGF1) regulates lifespan, metabolism, and stress resistance and is associated with neurodegenerative diseases and the aging process. Loss of this pathway leads to diabetes, but can lead to an increase in life expectancy and a decrease in the aggregation of toxic proteins. In a recent paper by Cohen E and Dillin A of The Salk Institute for Biological Studies, "The Insulin Paradox: Aging, Protein Toxicity, and Neurodegenerative Diseases," the authors discuss this paradox and the therapeutic potential for influencing this signaling pathway for treating neurodegenerative diseases.

Age and hormone-associated cancer

As you know, the incidence of oncological diseases increases with age. Age-associated tumor types are considered to be prostate cancer, breast cancer, uterine adenocarcinoma, ovarian cancer, pancreatic cancer, and thyroid cancer. Consider the most common adult cancer, breast cancer. in women, breast cancer occurs at least 100 times more often than in men, has long forced researchers to admit that the assessment of the state of the reproductive system is one of the important approaches to studying the pathogenesis of this tumor. This, in particular, is reflected in the fact that among the risk factors for breast cancer, the significance of which has been confirmed by multiple and multicenter epidemiological studies, along with the presence of the same disease in blood relatives and previous biopsies for benign processes in the gland, early onset of menarche is presented. , late menopause and late first childbirth. (On this basis, a number of models have been built to predict in numerical terms the individual risk of developing the disease in "carriers" of the listed stigmas - Gail et al., 1989.) However, it should be emphasized that if the combination of early first menstruation and late menopause is, in particular, a reflection a longer reproductive period (and, accordingly, a longer hormonal stimulation of the mammary gland), then late first childbirth, as a rule, is regarded from different positions - a delayed completion of the full functional maturation of the organ. In this regard, it is emphasized that the differentiation of the cellular elements of the mammary gland, starting from adolescence, reaches its peak after the first birth and lactation, followed by a regression during menopause. An important characteristic of these changes is the ratio of primitive ducts, classified as lobules 1 and 2, and differentiated glandular structures (lobules 3 and 4), which together make up the so-called terminal duct-lobular units. It is believed that a higher level of proliferation in lobules 1 and 2 is the result of their higher sensitivity to hormonal stimulation, and, as a consequence, in these lobules more often than in lobules 3 and 4, signs of atypia or carcinoma in situ are found (Russo, Russo , 1997). In these examples, one can see the intersection of several "vectors", in particular, what should be the state of the target tissue, which hormones are capable of exerting a problastomogenic effect on it, and at what age they act most effectively in this regard (i.e. promote cell regeneration). With regard to the latter issue, considerable attention is currently being paid to the perinatal and especially the intrauterine period of life. It is assumed that at this moment, a kind of stem cells are "selected" that are least resistant to adverse hormonal influences in utero and are capable of further, undergoing hormonal stimulation already in adulthood, acquiring the features of true tumor cells (Adami et al., 1995). At the same time, markers of pre- / perinatal predisposition to the development of breast cancer are birth with a large mass, jaundice of newborns, the absence of toxicosis of pregnancy, etc., and their true equivalents, which may be important in the pathogenesis of the disease, are excessive intrauterine production of estrogens and growth factors such as IGF-1 (Michels et al., 1996; Bershtein, 1997; Ekbom et al., 1997). The influence of these hormones and hormone-like factors can be faster or, conversely, delayed, creating conditions for the emergence of various pathogenetic variants of breast cancer and confirming the importance of the age (temporary) factor in this disease (Semiglazov, 1980, Semiglazov, 1997; Dilman, 1987 ). The clinical reflection of this situation is, first of all, the existence of pre- and postmenopausal forms of breast cancer and two more or less distinct age-specific peaks in incidence, separated by about a decade in time. Pre- and postmenopausal variants of the disease differ not only in a number of clinical features, but also in the frequency of detection of certain epidemiological risk factors, and in the spectrum of hormonal-metabolic disorders. A typical example is the role of overweight and differences in its composition (in the ratio of "fat / lean weight") at the same body weight: a large weight and an increase in the proportion of body fat increase the risk of developing postmenopausal breast cancer and, on the contrary, " protect "from the emergence of its premenopausal variant (Bershtein, 1997). Obesity is characterized by deviations in various endocrine homeostats, and, accordingly, insulin resistance is one of those parameters that, along with impairments in steroid production, is currently regarded as one of the leading predisposition factors for the development of breast cancer (Bruning et al., 1992; Gamayunova et al. ., 1987). The difference in this respect between insulin and IGF-1 is that, prospectively, excess IGF-1 in circulation predisposes to premenopausal breast cancer (Hankinson et al. , 1998), while hyperinsulinemia and insulin resistance increase the risk of developing both forms of the disease (Bruning et al., 1992). The accelerated growth of the body in length during puberty acts similarly to the last two factors (Berkey et al., 1999).

Turning back to steroids, it should be noted that the increased risk of breast cancer is determined not only by estrogens and their excessive stimulation of the target tissue. According to some reports, the increase in the incidence of breast cancer in women who received a combination of estrogens and progestins in menopause is almost the same as in women treated with estrogens alone, or even higher than in the latter (Schairer et al., 2000); this is consistent with the notion that progesterone has a mitogenic effect on the mammary epithelium (Pike, 1987; Henderson et al., 1997). The association of androgens with the same problem manifests itself in two main respects: the risk of developing breast cancer, in accordance with some, but not all, available prospective studies, is facilitated, on the one hand, by a decrease in the production of adrenal androgens, in particular dehydroepiandrosterone sulfate (which coincides with the previous conclusions about the significance of the so-called Balbrook discriminant - Bulbrook et al., 1971, and, on the other hand, an excess of predominantly gonadal androgens such as testosterone (Cauley et al., 1999). It is possible that the noted, albeit inconsistent, multidirectional changes may be due to the different effect of insulin on the production of androgens in the gonads and adrenal cortex, which, in turn, is additional evidence of the combined involvement of steroid and peptide hormones in the analyzed process.Another confirmation of this is the recently presented results of prospective observations, in which there is a directly proportional relationship between the level of prolactin in plasma and the subsequent development of breast cancer (Hankinson et al., 1999).
In a recent article by Svetlana Ukraintseva et al. from Center for Population Health and Aging 5) Hormonal aspects of age-associated diseases and many others.

The main changes in endocrine functions in old age are: 1) a gradual decrease in the synthesis, secretion and level of most hormones in the blood; 2) increasing the sensitivity of tissues to the effects of low doses of hormones; 3) a decrease in the reactivity of target organs to the effects of large doses of most hormones, 4) a decrease in the effectiveness of self-regulation mechanisms in the endocrine system, mainly due to the weakening of feedbacks in the regulatory system, 5) low efficiency and rapid depletion of adaptive responses provided by the endocrine system.

Physiological features of the endocrine system in old age determine the risk of developing the following major disorders in the body: 1) predisposition to the development of diabetes mellitus and thyroid dysfunction, 2) the appearance of unusual, "ectopic" hormone production, usually of a tumor nature, 3) a tendency to calcium disorders metabolism associated with a deficiency of sex steroids, age-related decrease in the intake of vitamin D into the body, disorders of intestinal absorption, changes in the nature of nutrition, 4) hormonal imbalance due to age-related characteristics of the pharmacokinetics and pharmacodynamics of drugs.

The only endocrine disorders that do not occur in old age relate to endocrine shifts during menstruation, puberty and pregnancy.

Neuroendocrine systems. Secretion Neurosecretory elements of the anterior hypothalamus undergo degenerative changes in old age. In neurosecretory neurons, the size of the nucleus decreases, the content of DNA, RNA and protein renewal decreases. In many of them, the removal of the neurosecret is weakened. The content of somatoliberin and corticoliberin in the hypothalamus decreases with aging. In the pituitary gland and blood, the content of thyrotropin and corticotropin decreases. The level of gonadotropin in old age slightly increases, which is apparently associated with the activation of neuroendocrine mechanisms according to the feedback principle under conditions of a decrease in the production of sex steroids in the gonads. The ratio of gonadotropins also changes with aging. Thus, the content of follitropin in men increases almost 4 times with aging and significantly exceeds the degree of increase in the level of lutropin, which is due to age-related insufficiency in the testes of the hormone inhibin, which inhibits the production of follitropin in the pituitary gland by the feedback mechanism. The cessation of sexual cyclicity in women is due to a decrease in the secretion of estrogen by the ovaries and, accordingly, their induction of preovulatory lutropin emissions. As women age, the sensitivity of the hypothalamic centers for the regulation of gonadotropin secretion to the inhibitory effect of estrogens also decreases.

Aging and male sex hormones . The decline in testosterone levels (Fig. 2-5) in men with aging is primarily due to testicular factors. So, in the testes of an aging man, the number of Leydig cells decreases, the blood supply to the testicles decreases, and the biosynthesis of steroids is disrupted. With age, the sensitivity of the structures of the hypothalamic-pituitary system, which perceive the effects of testosterone through a feedback mechanism, changes. Thus, the inhibitory effect of the introduction of exogenous androgens into the blood on the secretion of lutropin in elderly men is enhanced. The disappearance of daily fluctuations in the concentration of testosterone in the blood plasma, which took place in adulthood, also testifies to the age-related changes in the hypothalamic-pituitary system. At the same time, the frequency of large impulse emissions of lutropin into the blood decreases. The opioidergic effects on the production of gonadoliberins are weakened. A slight increase in the level of estrogen in the blood of older men is associated with an increase in the conversion of testosterone into estrone and estradiol. Estrogens reduce their sensitivity of adenohypophysis gonadotrophs to the action of gonadoliberin, stimulate the formation of testosterone-binding globulin in the liver and secretion into the blood, reducing the concentration of biologically active testosterone. These shifts lead to the feminization of the aging organism. The cellular reception of androgens also decreases with aging, which is one of the reasons for the weakening of the synthesis of androgen-dependent proteins. The decline in testicular function with age is accelerated under the influence of stress, alcoholism, tobacco smoking, acute and chronic diseases.

Aging and female sex hormones . In women, when menopause is established, the inhibitory effects of sex steroids and inhibin on the production of gonadotropins disappear and the level of lutropin and, especially, follitropin in the blood increases. The hypothalamic generator of impulse secretion of gonadotropins continues to function and determines its high amplitude, while the daily production of follitropin in postmenopausal women is 10 times higher than during the follicular phase of young women, and the production of lutropin is 3 times higher. After 70 years in women, the level of gonadotropins, the frequency and amplitude of their impulse secretion decrease.

The first 3-4 years after menopause, the ovaries continue to secrete some amounts of estrogen, at a later date, adipose and muscle tissues become the source of blood estrogens, where the aromatization of androstenedione secreted by the adrenal glands occurs. The cellular reception of estrogens in the reproductive organs also decreases with age. However, estrogens in the senile organism play an important physiological role - they inhibit bone tissue lysis and the development of osteoporosis. Stress, especially short-term, unlike men, does not lead to inhibition of the formation of estrogens, and may even increase their level in the blood. The latter is explained by the higher resistance of women to the effects of unfavorable environmental factors on the body and their longer life expectancy.

Aging and the hypothalamic-pituitary system . With aging of the body, there is a loss of the pulsating nature of the secretion of hormones of the adenohypophysis: somatotropin and thyrotropin.

In old age, muscle mass decreases, the strength and speed of muscle contractions decrease, and part of the muscle tissue is replaced with adipose tissue. Decreased levels of growth hormone may be the cause of these changes. Moderate physical activity even in people over 80 years of age has a beneficial effect on muscle tissue mass and muscle function, significantly weakening the age-related decrease in growth hormone secretion. At the same time, heavy one-time physical activity leads to an increase in the blood level of growth hormone up to 18 times!

Growth hormone, the main hormone regulating growth in childhood, has a number of metabolic effects at a young age - anabolic, lipolytic, diabetogenic. The secretion of this hormone is pulsating and constant. Starting from the age of 30, the secretion of pituitary growth hormone tends to decrease. After 55 years, the total daily level of the hormone concentration in the blood is 1/3 lower than in people 18-33 years old, and the nighttime pulsation of its secretion becomes weaker and disappears with aging by the age of 70. This age-related growth hormone deficiency is due to decreased secretion of hypothalamic somatoliberin, hypersecretion of somatostatin, or decreased pituitary sensitivity to somatoliberin.

The content in blood and tissues of insulin-like growth factor or somatomedin (mainly of hepatic origin) is also reduced in old age. At the same time, the degree of decrease in the level of the hormone correlates with age: by 11% at 40-50 years old, by 20% at 50-60 years old, by 22% at 60-70 years old, by 55% at 80-90 years old and corresponds to the degree of fatty degeneration. skeletal muscle. The effects of growth hormone deficiency, such as atrophy of muscle tissue mass and its fatty degeneration, are reversible under the influence of restorative doses of the hormone (this can be done through the formation of recombinant DNA) in experimental animals and people over the age of 50. By introducing somatotropin into the body for several months, 60-80-year-olds with a reduced blood level of the hormone for their age norm can increase the concentration of somatomedin to the level of young people. An artificial increase in the content of the latter in the elderly leads to an increase of 10% in "fat-free" body weight and a decrease in 15% of the mass of adipose tissue. After such a replacement of the hormone deficiency in old people, the strength of the bones of the spine, skin elasticity, physical endurance, isometric muscle strength and the rate of basal metabolism increased. At the same time, side effects in such people were also noted: an increase in fasting blood glucose and insulin levels. Taking into account the possible side effects of the administration of somatotropin to the elderly on glucose metabolism (up to diabetes), dysfunction of the joints (up to arthritis) and the cardiovascular system (up to arterial hypertension), a promising, but relatively moderate, effect of this hormone on skeletal muscle gives reason to be critical of the use of growth hormone in the elderly for therapeutic purposes. Nevertheless, the result of even partial restoration of muscle mass and function in them testifies to the ability of tissue cells to respond to hormonal stimulation that persists in old age. In old age, many tissues, including muscle, need more growth hormone not for growth, but to stabilize the required level of protein synthesis in them.

In old people, the ability for prolonged activation of the hypothalamic-pituitary system decreases, which significantly narrows the range of adaptive reactions of the body. The sensitivity of the adrenal cortex to the action of corticotropin in old age is increased, however, prolonged administration of exogenous corticotropin to the body of old animals leads to depletion of the adrenal cortex faster. Consequently, in old age, the biological reliability of the hypothalamic-pituitary system is reduced, the secretion of its hormones is more likely to be depleted.

Under stress, the secretion of cortisol in old age can be inadequately high. This is due to dysfunction of the central, mainly hypothalamic glucocorticoid receptors and weakening of the feedback in the hypothalamic-pituitary-adrenal system. In combination with low secretion of sex steroids and growth hormone, these changes can lead to disturbances in psychological status, well-being, insulin resistance and other risk factors for diseases characteristic of an aging person. Often, these hormonal shifts occur earlier than the calendar old age, reflecting the processes of premature aging.

The level of prolactin in the blood in the elderly is usually increased.

Thyroid function . The level of thyroid activity decreases with age, which is due to both a decrease in thyrotropin production and age-related changes in the gland itself. The thyrotropic activity of the pituitary gland in humans is maximal at the age of 20-30 years, and by the age of 60-80 years of life, it almost halves. The sensitivity of the thyroid gland to small doses of thyrotropin is increased, which makes it possible to maintain a certain level of its activity in old age, but large doses of the hormone activate the thyroid gland weaker than at a young age. In the blood of an old person, a redistribution of forms of activity of thyroid hormones occurs - the number of bound forms decreases, and the free forms of the hormone practically do not change, which also contributes to maintaining the level of thyroid effects necessary for the body. In target tissues, the sensitivity to low doses of thyroid hormones increases, but their reactivity to high doses decreases, which is generally typical of old age. The general change in thyroid activity in old age is obviously responsible for the weakening of protein synthesis, impaired fat metabolism, the development of atherosclerosis, and changes in the autonomic nervous regulation of internal organs. Therefore, hypofunction of the thyroid gland was considered the leading mechanism of aging at one time.

Adrenal medulla . With aging, the synthesis of catecholamines decreases and the pathways of their metabolic conversion are redistributed. In the adrenal glands, the adrenaline content is halved, and the total level of blood catecholamines also decreases. At the same time, compared to adulthood, the concentration of norepinephrine in the blood is reduced by 6-7 times, which depends on the degree of decrease in the activity of the sympathetic nervous system. At the same time, the synthesis of the mediator and its reuptake by the presynaptic endings are reduced. There is also a redistribution of the pathways of postsynaptic transformation of the mediator - the activity of monoamine oxidase increases and the activity of catechol-o-methyltransferase decreases. The transition of catecholamines from the blood to tissues is slowed down both due to their low concentration and as a result of the weakening of the tissue's ability to bind catecholamines. Accordingly, with a decrease in the synthesis, blood concentration and metabolism of catecholamines in old age, the content in the urine of the main decay product of catecholamines, vanilla-mandelic acid, is reduced. Under stressful influences on the body in the blood of old people, the level of adrenaline increases significantly less than in adults. At the same time, at this age, sensitivity increases and the reactivity of tissues to adrenaline decreases. Thus, in experiments on animals with the introduction of small doses of the hormone, shifts in the level of blood sugar, blood pressure, vascular tone of the extremities and kidneys, excitation of angioreceptors, changes in glycolysis, glycogenolysis and oxidative phosphorylation in the myocardium in old animals are more pronounced than in young animals. However, with the introduction of large doses of adrenaline, functional and metabolic changes are more pronounced in young animals.

Sugar-regulating hormones.

The regulation of blood glucose is a function of the body with many alternative control mechanisms and therefore remains stable in most seniors. Similar stability with aging applies to acid-base control and other functions with multiple regulatory mechanisms. At the same time, the maintenance of a normal glycemic level in old age is impaired: the level of fasting blood glucose gradually increases with aging, tests for detecting glucose tolerance show that after oral administration of sugar, the glucose level is higher and longer remains elevated in the elderly compared to young people. The progressive decrease in glucose tolerance with aging is associated with an increase in cell resistance to insulin and a decrease in the number of insulin receptors and its membrane transporters. Consequently, latent insulin deficiency is formed in old age. With aging, the content of substances that inhibit the activity of insulin also increases in the blood. At the same time, insulinase activity in the liver decreases compensatory, which allows maintaining the level of insulin in the blood. In the process of aging, the reliability of the functioning of the insulin regulation system decreases, which creates the preconditions for the development of impaired glucose tolerance and the occurrence of diabetes mellitus.

Calcium-regulating hormones.

A decrease in bone mass during aging as a result of a decrease in calcium content in bones is a natural phenomenon (Fig. 2-6). The factors that determine the peak bone mass are subdivided into genetic and non-genetic (nutrition, smoking, physical inactivity and physical activity, hypogonadism, etc.).

Factors that reduce bone mass in the elderly are age-related changes in the level of calcium-regulating and sex hormones, menopause and the accompanying estrogen deficiency, lifestyle (dietary habits leading to vitamin D and calcium deficiencies, alcohol consumption, tobacco smoking, physical inactivity, drugs that violate balance of calcium, such as caffeine).

Approximately 60% of elderly people are characterized by a relative deficiency in vitamin D. Most of them show signs of weakening bone mineralization and increased metabolic turnover of calcium in bone tissue, which is due to some hyperparathyroidism in conditions of vitamin D deficiency. Deficiency of the latter plays a pathogenetic role in the origin of senile osteoporosis , which dictates the need to artificially maintain the level of cholecalciferol (calcitriol) in the blood of the elderly. In old age, the frequency of hyperparathyroidism also increases, amounting to 1-2 cases per 90 elderly people, which is one of the main risk factors for bone fractures in them. Senile osteoporosis develops much faster under the influence of chronic alcohol use, tobacco smoking, excess caffeine intake, hypokinesia. The more a healthy lifestyle is disturbed, the more often and more pronounced is senile osteoporosis. Postmenopausal osteoporosis and hip fractures occur after 60 years 1.5-2 times more often in women who drink more than 2 glasses of coffee a day.

Postmenopausal osteoporosis, as a rule, leads to the release of lead contained in the bone tissue into the blood, which can lead to the manifestation of its toxic effect in tissues, which accelerates the aging process.

Aging and risk factors.

Age-related changes in the function of the endocrine system during aging are one of the reasons for the increase in the number of risk factors for health disorders in old age, many of the latter lead to accelerated aging of the body. Thus, tobacco smoking is one of the factors accelerating the aging process, which is associated with the progression of tissue blood supply disorders and hypoxia. Overnutrition - a powerful risk factor in old age - also accelerates the aging process. This is due to the fact that excessive intake of nutrients in the body leads not only to obesity, but also causes the development of metabolic syndrome with insufficiency of the insular apparatus, atherosclerosis, arterial hypertension and coronary heart disease.

The neuroendocrine rearrangements arising in old and senile age in the form of weakening of connections in the systems of the hypothalamus - adenohypophysis - endocrine glands (gonads, adrenal glands, thyroid gland) cause a decrease in the adaptive abilities of the organism. The adaptive value of the general adaptation syndrome also weakens with aging. With prolonged or repeated stresses in old age, the stage of depletion of stress and inhibition of the adaptive reactions of the body begins faster. Prolonged stress leads in old age to a rapid decrease in the secretory function of the adrenal glands and, accordingly, in the excretion of corticosteroids. The adaptive capabilities of the senile organism are largely provided by a decrease in its reactivity to the action of stress factors. However, the aging process leads not only to a quantitative change in the adaptive abilities of the organism, the qualitative nature of adaptation also changes. If in adulthood, hypothalamic activation is mainly based on noradrenergic mechanisms, then in old age psychoemotional and painful stress leads to activation of serotonergic mechanisms. These changes in mediator substances during stress in old age do not affect the posterior part of the hypothalamus, they are detected only in the anterior and middle parts, whereas in adulthood, noradrenergic mechanisms are activated in all three of its parts. The dopaminergic mechanisms of the hypothalamus are involved in the regulation of aldosterone secretion during stress in old age.

With aging, the level of aldosterone in the blood tends to decrease compared to the concentration of the hormone in adulthood. At the same time, the use of a hypocaloric diet in experiments on animals with the aim of prolonging their life was accompanied by a stable increase in the concentration of aldosterone in the blood, which, under conditions of a decrease in the cellular reception of the hormone and its binding to tissues in old age, has an adaptive character, because is aimed at regulating the homeostasis of potassium and sodium ions.

With aging, the secretion and level of vasopressin in the blood increase, the sensitivity of tissues to the hormone increases, which can serve as a risk factor for the development of pathology of water-salt metabolism and arterial hypertension, because the increase in vasopressin secretion in acute stress in old age is increased. The increased activity of the vasopressin stress response is promoted by physiological hypothyroidism of old age.

The activity of the renin-angiotensin system decreases with aging, however, in old age the sensitivity of the renin-angiotensin system to low-intensity loads is increased, while submaximal loads cause a less pronounced and lasting effect of activating this system than at a young age.

Thus, in old age, the body's sensitivity to stress is increased, but the resistance of adaptation, due to the duration of the adaptive reactions of the endocrine system, is significantly reduced. In acute stress caused by hypoglycemia or myocardial infarction, the decrease in testosterone levels in the blood of older men is less pronounced than at a young age. In older women, psycho-emotional stress causes a marked decrease in the level of estrogen in the blood, which can contribute to senile osteoporosis.

The higher psychoemotional sensitivity of older people to stress causes them to develop alcoholism more often. The characteristic changes in the psyche and emotional behavior of older people with chronic alcoholism may be associated with the accumulation of somatostatin in the striatum and hippocampus.

Chronic alcohol consumption in old age leads to significantly higher blood levels of insulin-like growth factor compared to nondrinking older people. Aging and alcohol increase the sensitivity of mitochondria to the damaging effects of intracellular excess calcium. This effect is attenuated by glucagon.

The increase in blood norepinephrine and sympathetic activity after age 60 may be largely due to tobacco smoking. If they have a duodenal ulcer, even in history, the age-related increase in the level of norepinephrine in the blood is more pronounced. These people are more sensitive to stress than the general population of the corresponding age, and they are more susceptible to the development of diseases associated with tobacco smoking. Under stress in old age, tobacco smoking can cause more severe consequences and cause the development of cardiovascular diseases or peptic ulcer disease rather than hypersecretion of the stress hormones cortisol and adrenaline. The combination of the negative effects of tobacco smoking and the effects of stress hormones increases the possibility of developing pathology of the cardiovascular system and other harmful effects of stress (peptic ulcer disease, malignant tumors, diabetes mellitus) in old age. The combination of smoking and stress is a leading risk factor for developing cataracts associated with sclerosis of the lens nucleus.

Tobacco smoking in postmenopausal women contributes to an increase in their blood lead concentration. The postmenopausal period, as noted above, is characterized by an increased release of lead from bone depots into the blood. Tobacco smoking and postmenopausal changes in hormonal regulation of bone tissue mutually enhance the effect of increasing blood lead levels. Women who have not had a pregnancy in their life differ in the postmenopausal period by a significantly higher level of lead in the blood, from women who had a previous pregnancy. This difference is especially pronounced in them when they smoke tobacco. The early postmenopausal period (about 4 years) is characterized by higher blood lead levels than later periods. Thus, tobacco smoking in elderly women is a risk factor for the toxic effect of lead on the enzyme systems of body cells.

Endocrine system n 1. Endocrine glands n Pituitary gland (adenohypophysis and neurohypophysis) n ADrenal glands (cortex and medulla) n Thyroid gland n Peri-glandular glands n EPIPHYSIS n 2. Organs with endocrine glandular tissue n SUBGUMINOUS endocrine function of cells n PLACENTA n THYMUS n KIDNEY n HEART

General properties of the endocrine glands: n 1) the absence of external ducts, the hormones produced go directly into the blood; n 2) small size and weight of the glands; n 3) exposure in low concentrations; n 4) selectivity of hormones action; n 5) the specificity of the caused functional effects; n 6) rapid destruction of hormones.

The chemical nature of hormones n steroid - sex hormones and hormones of the adrenal cortex; n derivatives of amino acids - hormones of the adrenal medulla, thyroid gland; n protein-peptide hormones - hormones of the pituitary gland, pancreas, parathyroid glands, as well as hypothalamic neuropeptides.

MALE SEX HORMONES TESTOSTERONE, ANDROSTERONE Sexual differentiation in ontogenesis Regulation of sexual behavior Development of sexual characteristics Regulation of spermatogenesis Anabolic effect on the skeleton and body muscles Retention of nitrogen, K, P and calcium in the body Activation of RNA synthesis Stimulation of erythropoiesis

FEMALE SEX HORMONES ESTROGENS Sexual differentiation in embryogenesis, puberty, development of female sexual characteristics, establishment of the menstrual cycle Growth of uterine muscle and epithelium, stimulation of the proliferative phase of the cycle Regulation of sexual behavior Increase of uterine contractility and its sensitivity to oxytocin Weakening of the readiness of the uterus to contract Activation of the secretory structures of the endometrium Activation of the growth of the mammary glands Suppression of the secretion of gonadotropins by the pituitary gland

The negative effect of excessive release of glucocorticoids leads to negative effects: n decreases immunity (production of antibodies and lymphocytes decreases, the intensity of phagocytosis); n increases the risk of stomach ulcers as a result of activation of the secretion of hydrochloric acid and pepsin in the stomach; n at high concentrations, glucocorticoids behave like aldosterone and activate the process of reabsorption of water and sodium ions, cause their retention in the body, which leads to an increase in blood pressure; n increase the sensitivity of vascular smooth muscles to catecholamines, which leads to vasospasm, especially small ones, and, accordingly, to an increase in blood pressure; n cause demineralization of bones, loss of calcium in the urine, reduce the absorption of calcium in the intestine; n As a result of active gluconeogenesis, the process of protein synthesis in skeletal muscles is inhibited and muscle weakness appears.

The endocrine system plays an important role in the regulation of body functions. The organs of this system - the endocrine glands - secrete special substances that have a significant and specialized effect on the metabolism, structure and function of organs and tissues (see Fig. 34). The endocrine glands differ from other glands that have excretory ducts (excretory glands) in that they secrete the substances they produce directly into the blood. Therefore, they are called endocrine glands (Greek endon - inside, krinein - to excrete).

Fig. 34. Human endocrine system

The child's endocrine glands are small in size, have a very small mass (from fractions of a gram to several grams), and are richly supplied with blood vessels. Blood brings the necessary building materials to them and carries away chemically active secrets.
An extensive network of nerve fibers approaches the endocrine glands, their activity is constantly monitored by the nervous system. By the time of birth, the pituitary gland has a distinct secretory activity, which is confirmed by the presence of a high ACTH content in the umbilical cord blood of the fetus and newborn. The functional activity of the thymus and adrenal cortex in the uterine period has also been proven. The development of the fetus, especially at an early stage, is undoubtedly influenced by the mother's hormones, which the child continues to receive with breast milk in the extrauterine period. In the biosynthesis and metabolism of many hormones in newborns and infants, there are features of the prevailing influence of one specific endocrine gland.

The endocrine glands secrete physiologically active substances into the internal environment of the body - hormones that stimulate or weaken the functions of cells, tissues and organs.

Thus, the endocrine glands in children, along with the nervous system and under its control, ensure the unity and integrity of the body, forming its humoral regulation. The concept of "internal secretion" was first introduced by the French physiologist C. Bernard (1855). The term "hormone" (Greek hormao - excite, induce) was first proposed by the English physiologists W. Beilis and E. Starling in 1905 for secretin, a substance formed in the mucous membrane of the duodenum under the influence of hydrochloric acid of the stomach. Secretin enters the bloodstream and stimulates the secretion of juice by the pancreas. To date, more than 100 different substances have been discovered, endowed with hormonal activity, synthesized in the endocrine glands and regulating metabolic processes.

Despite the differences in the development, structure, chemical composition and action of hormones of the endocrine glands, they all have common anatomical and physiological features:

1) they are non-flowing;

2) consist of glandular epithelium;

3) are abundantly supplied with blood, which is due to the high intensity of metabolism and the release of hormones;

4) have a rich network of blood capillaries with a diameter of 20-30 microns or more (sinusoids);

5) are equipped with a large number of autonomic nerve fibers;

6) represent a single system of endocrine glands;

7) the leading role in this system is played by the hypothalamus ("endocrine brain") and the pituitary gland ("the king of hormonal substances").

In the human body, there are 2 groups of endocrine glands:

1) endocrine, performing the function of only the organs of internal secretion; these include: pituitary gland, pineal gland, thyroid gland, parathyroid glands, adrenal glands, neurosecretory nuclei of the hypothalamus;

2) glands of mixed secretion, having an endo- and exocrine part, in which the secretion of hormones is only part of the various functions of the organ; these include: pancreas, sex glands (gonads), thymus gland. In addition, other organs that are not formally related to the endocrine glands have the ability to produce hormones, for example, the stomach and small intestine (gastrin, secretin, enterocrinin, etc.), the heart (natriuretic hormone - auriculin), kidneys (renin, erythropoietin), placenta (estrogen, progesterone, chorionic gonadotropin), etc.

The main functions of the endocrine system

The functions of the endocrine system are to regulate the activity of various body systems, metabolic processes, growth, development, reproduction, adaptation, and behavior. The activity of the endocrine system is based on the principles of hierarchy (subordination of the peripheral link to the central one), "vertical direct feedback" (enhanced production of a stimulating hormone with a lack of hormone synthesis at the periphery), a horizontal network of interaction of peripheral glands with each other, synergism and antagonism of individual hormones, reciprocal autoregulation.

Characteristic properties of hormones:

1) specificity of action - each hormone acts only on certain organs (“target” cells) and functions, causing specific changes;

2) high biological activity of hormones, for example, 1 g of adrenaline is enough to enhance the activity of 10 million isolated frog hearts, and 1 g of insulin - to lower blood sugar levels in 125 thousand rabbits;

3) distant action of hormones. They affect not the organs where they are formed, but organs and tissues located far from the endocrine glands;

4) hormones have a relatively small molecular size, which ensures their high penetrating ability through the capillary endothelium and through the membranes (membranes) of cells;

5) rapid destruction of hormones by tissues; for this reason, in order to maintain a sufficient amount of hormones in the blood and the continuity of their action, their constant release by the corresponding gland is necessary;

6) most hormones have no species specificity, therefore, in the clinic, it is possible to use hormonal preparations obtained from the endocrine glands of cattle, pigs and other animals;

7) hormones act only on processes occurring in cells and their structures, and do not affect the course of chemical processes in a cell-free environment.

Pituitary gland in children , or the lower appendage of the brain, is most developed at the time of birth, is the most important "central" endocrine gland, since with its triple hormones (Greek tropos - direction, turn) it regulates the activity of many other, so-called "peripheral" endocrine glands (see Fig. 35). It is a small oval gland weighing about 0.5 g, increasing to 1 g during pregnancy. It is located in the pituitary fossa of the Turkish saddle in the body of the sphenoid bone. With the help of the leg, the pituitary gland is connected to the gray puff of the hypothalamus. Its functional feature is versatility of action.

Fig. 35. Location of the pituitary gland in the brain

In the pituitary gland, there are 3 lobes: anterior, intermediate (middle) and posterior lobes. The anterior and middle lobes are of epithelial origin and are combined into the adenohypophysis, the posterior lobe, together with the pituitary stalk, is neurogenic in origin and is called the neurohypophysis. The adenohypophysis and the neurohypophysis differ not only structurally, but also functionally.

AND. Anterior lobe the pituitary gland makes up 75% of the mass of the entire pituitary gland. Consists of the connective tissue stroma and epithelial glandular cells. 3 groups of cells are distinguished histologically:

1) basophilic cells secreting thyrotropin, gonadotropins and adrenocorticotropic hormone (ACTH);

2) acidophilic (eosinophilic) cells that produce growth hormone and prolactin;

3) chromophobic cells - reserve cambial cells, differentiating into specialized basophilic and acidophilic cells.

Functions of the tropic hormones of the anterior pituitary gland.

1) Growth hormone (growth hormone, or somatotropic hormone) stimulates protein synthesis in the body, the growth of cartilage tissue, bones and the whole body. With a lack of growth hormone in childhood, dwarfism develops (growth less than 130 cm in men and less than 120 cm in women), with an excess of growth hormone in childhood - gigantism (height 240-250 cm, see Fig. 36), in adults - acromegaly (Greek .akros - extreme, megalu - large). In the postnatal period, STH is the main metabolic, affecting all types of metabolism and an active contrainsular hormone.

Fig. 36. Gigantism and dwarfism

2) Prolactin (lactogenic hormone, mammotropin) acts on the mammary gland, promoting the growth of its tissue and milk production (after the preliminary action of female sex hormones on it: estrogen and progesterone).

3) Thyrotropin (thyroid-stimulating hormone, TSH) stimulates the function of the thyroid gland, carrying out the synthesis and secretion of thyroid hormones.

4) Corticotropin (adrenocorticotropic hormone, ACTH) stimulates the formation and secretion of glucocorticoids in the adrenal cortex.

5) Gonadotropins (gonadotropic hormones, HT) include folli-tropin and lutropin. Follitropin (follicle-stimulating hormone) acts on the ovaries and testes. Stimulates the growth of follicles in the ovary of women, spermatogenesis in the testes in men. Lutropin (luteinizing hormone) stimulates in women the development of the corpus luteum after ovulation and the synthesis of progesterone by it, in men - the development of interstitial tissue of the testicles and the secretion of androgens.

B. Average share the pituitary gland is represented by a narrow strip of epithelium, separated from the posterior lobe by a thin layer of loose connective tissue. Adenocytes of the middle lobe produce 2 hormones.

1) Melanocyte-stimulating hormone, or intermedin, affects pigment metabolism and leads to darkening of the skin due to the deposition and accumulation of melanin pigment in it. With a lack of inter-medin, skin depigmentation (the appearance of skin areas that do not contain pigment) can be observed.

2) Lipotropin enhances lipid metabolism, affects the mobilization and utilization of fats in the body.

IN. Posterior lobe The pituitary gland is closely associated with the hypothalamus (hypothalamic-pituitary system) and is formed mainly by ependyma cells called pituicites. It serves as a storage reservoir for the hormones vasopressin and oxytocin, which are transported here along the axons of neurons located in the hypothalamic nuclei, where the synthesis of these hormones is carried out. The neurohypophysis is not only a place of deposition, but also a kind of activation of hormones coming here, after which they are released into the blood.

1) Vasopressin (antidiuretic hormone, ADH) has two functions: it enhances the reabsorption of water from the renal tubules into the blood, increases the tone of vascular smooth muscle (arterioles and capillaries) and increases blood pressure. With a lack of vasopressin, diabetes insipidus is observed, and with an excess of vasopressin, complete cessation of urination may occur.

2) Oxytocin acts on smooth muscles, especially the uterus. It stimulates the contraction of the pregnant uterus during labor and the expulsion of the fetus. The presence of this hormone is a prerequisite for the normal course of labor.

The regulation of the functions of the pituitary gland is carried out by several mechanisms through the hypothalamus, whose neurons simultaneously function as secretory and nerve cells. The neurons of the hypothalamus produce a neurosecretory containing releasing factors (releasing factors) of two types: liberins, which enhance the formation and secretion of tropic hormones by the pituitary gland, and statins, which inhibit (inhibit) the release of the corresponding tropic hormones. In addition, there is a bilateral relationship between the pituitary gland and other peripheral endocrine glands (thyroid, adrenal, gonads): the tropic hormones of the adenohypophysis stimulate the functions of the peripheral glands, and the excess of the latter's hormones suppresses the production and secretion of hormones of the adenohypophysis. The hypothalamus stimulates the secretion of tropic hormones of the adenohypophysis, and an increase in the concentration of tropic hormones in the blood inhibits the secretory activity of hypothalamic neurons. The autonomic nervous system has a significant effect on the formation of hormones in the adenohypophysis: its sympathetic division enhances the production of tropic hormones, the parasympathetic division inhibits.

Thyroid - an unpaired organ, shaped like a bow tie (see Fig. 37). It is located in the anterior region of the neck at the level of the larynx and upper trachea and consists of two lobes: right and left, connected by a narrow isthmus. From the isthmus or from one of the lobes, a process extends upward - a pyramidal (fourth) lobe, which occurs in about 30% of cases.

Fig. 37. Thyroid

In the process of ontogenesis, the mass of the thyroid gland increases significantly - from 1 g in the neonatal period to 10 g by 10 years. With the onset of puberty, the growth of the gland is especially intense. The mass of the gland is not the same for different people and varies from 16-18 g to 50-60 g. Women have more weight and volume than men. The thyroid gland is the only organ synthesizing organic substances containing iodine. Outside, the gland has a fibrous capsule, from which partitions extend inward, dividing the substance of the gland into lobules. In the lobules between the layers of connective tissue are follicles, which are the main structural and functional units of the thyroid gland. The follicle walls consist of a single layer of epithelial cells - cubic or cylindrical thyrocytes located on the basement membrane. Each follicle is surrounded by a network of capillaries. The cavities of the follicles are filled with a viscous mass of slightly yellow color, which is called a colloid, consisting mainly of thyroglobulin. The glandular follicular epithelium has a selective ability to accumulate iodine. In the tissue of the thyroid gland, the concentration of iodine is 300 times higher than its content in the blood plasma. Iodine is also contained in the hormones that are produced by the follicular cells of the thyroid gland - thyroxine and triiodothyronine. Up to 0.3 mg of iodine is released daily in the composition of hormones. Therefore, a person should receive iodine daily with food and water.

In addition to follicular cells, the thyroid gland contains the so-called C-cells, or parafollicular cells, secreting the hormone thyrocalcitonin (calcitonin), one of the hormones that regulate calcium homeostasis. These cells are located in the follicular wall or interfollicular spaces.

With the onset of puberty, the functional tension of the thyroid gland increases, as evidenced by a significant increase in the content of total protein, which is part of the thyroid hormone. The content of thyrotropin in the blood rapidly increases up to 7 years.
An increase in the content of thyroid hormones is noted by the age of 10 and at the final stages of puberty (15-16 years).

At the age of 5-6 to 9-10 years, the pituitary-thyroid relationship changes qualitatively - the sensitivity of the thyroid gland to thyroid-stimulating hormones decreases, the greatest sensitivity to which is noted at 5-6 years. This indicates that the thyroid gland is especially important for the development of the body at an early age.

The effect of thyroid hormones thyroxine (tetraiodothyronine, T4) and triiodothyronine (T3) on the child's body:

1) enhance the growth, development and differentiation of tissues and organs;

2) stimulate all types of metabolism: protein, fat, carbohydrate and mineral;

3) increase basal metabolism, oxidative processes, oxygen consumption and carbon dioxide emission;

4) stimulate catabolism and increase heat production;

5) increase motor activity, energy metabolism, conditioned reflex activity, the rate of mental processes;

6) increase heart rate, respiration, sweating;

7) reduce the ability of blood to clot, etc.

With hypofunction of the thyroid gland (hypothyroidism) in children, cretinism is observed (see Fig. 38) i.e. growth retardation, mental and sexual development, violation of body proportions. Early detection of thyroid hypofunction and appropriate treatment have a significant beneficial effect (Fig. 39).

Fig. 38 A child with cretinism

Figure: 39.Before and after treatment for hypothyroidism

Adults develop myxedema (mucous edema), i.e. mental retardation, lethargy, drowsiness; decreased intelligence, impaired sexual function, decreased basal metabolism by 30-40%. With a lack of iodine in drinking water, there may be an endemic goiter - an enlarged thyroid gland.

With hyperfunction of the thyroid gland (hyperthyroidism, see Fig. 40,41), a diffuse toxic goiter occurs - Graves' disease: weight loss, glitter of eyes, bulging, increased basal metabolism, excitability of the nervous system, tachycardia, sweating, feeling of heat, heat intolerance, increase in volume thyroid gland, etc.

Fig. 40. Graves' disease Fig. 41 Hyperthyroidism of the newborn

Thyrocalciotonin is involved in the regulation of calcium metabolism. The hormone lowers the level of calcium in the blood and inhibits its excretion from the bone tissue, increasing its deposition in it. Thyreocalciotonin is a hormone that preserves calcium in the body, a kind of calcium keeper in bone tissue.

Regulation of the formation of hormones in the thyroid gland is carried out by the autonomic nervous system, thyrotropin and iodine. Excitation of the sympathetic system enhances, and the parasympathetic - inhibits the production of hormones of this gland. The hormone of the adenohypophysis thyrotropin stimulates the formation of thyroxine and triiodothyronine. An excess of the latter hormones in the blood inhibits the production of thyrotropin. With a decrease in the level of thyroxine and triiodothyronine in the blood, the production of thyrotropin increases. A small amount of iodine in the blood stimulates, and a large amount inhibits the formation of thyroxine and triiodothyronine in the thyroid gland.

Parathyroid (parathyroid) glands are rounded or ovoid bodies located on the posterior surface of the thyroid lobes (see Fig. 42). The number of these bodies is variable and can vary from 2 to 7-8, on average 4, two glands behind each lateral lobe of the thyroid gland. The total mass of the glands ranges from 0.13-0.36 g to 1.18 g.

Fig. 42. Parathyroid glands

The functional activity of the parathyroid glands increases significantly by the last weeks of the prenatal period and in the first days of life. The hormone of the parathyroid glands is involved in the adaptation mechanisms of the newborn. In the second half of life, a slight decrease in the size of the main cells is found. The first oxyphilic cells appear in the parathyroid glands after 6-7 years of age, their number increases. After 11 years, an increasing number of fat cells appear in the gland tissue. The mass of the parenchyma of the parathyroid glands in a newborn is on average 5 mg, by the age of 10 it reaches 40 mg, in an adult - 75 - 85 mg. These data refer to cases where there are 4 or more parathyroid glands. In general, the postnatal development of the parathyroid glands is regarded as a slowly progressive involution. The maximum functional activity of the parathyroid glands refers to the perinatal period and the first - second years of life of children. These are periods of maximum intensity of osteogenesis and intensity of phosphorus-calcium metabolism.

The hormone-producing tissue is glandular epithelium: glandular cells - parathyrocytes. They secrete the hormone parathyrin (parathyroid hormone, or parathyrocrine), which regulates the exchange of calcium and phosphorus in the body. Parathyroid hormone helps maintain normal blood calcium levels (9-11 mg%), which is necessary for normal functioning of the nervous and muscular systems and calcium deposition in bones.

Parathyroid hormone affects the balance of calcium and, through a change in the metabolism of vitamin D, promotes the formation in the kidneys of the most active derivative of vitamin D - 1,25-dihydroxycholecalciferol. Calcium starvation or impaired absorption of vitamin D, underlying rickets in children, is always accompanied by hyperplasia of the parathyroid glands and functional manifestations of hyperparathyroidism, however, all these changes are a manifestation of a normal regulatory reaction and cannot be considered diseases of the parathyroid glands

There is a direct two-way relationship between the hormone-forming function of the parathyroid glands and the level of calcium in the blood. With an increase in the concentration of calcium in the blood, the hormone-forming function of the parathyroid glands decreases, and with a decrease, the hormone-forming function of the glands increases

With hypofunction of the parathyroid glands (hypoparathyroidism), calcium tetany is observed - seizures due to a decrease in the calcium content in the blood and an increase in potassium, which sharply increases excitability. With hyperfunction of the parathyroid glands (hyperparathyroidism), the calcium content in the blood increases above normal (2.25-2.75 mmol / l) and calcium deposition is observed in unusual places for it: in the vessels, aorta, kidneys.

Pineal gland, or pineal gland - a small oval glandular formation, weighing 0.2 g, related to the epithalamus of the diencephalon (see Fig. 43). It is located in the cranial cavity above the lamina of the midbrain roof, in the groove between its two upper mounds.

Figure: 43. Epiphysis

Most researchers who have studied the age-related characteristics of the pineal gland consider it to be an organ undergoing relatively early involution. Therefore, the pineal gland is called the gland of early childhood. With age, in the pineal gland there is an increase in connective tissue, a decrease in the number of parenchymal cells, and depletion of the organ with vessels. These changes in the human pineal gland begin to be detected from 4-5 years of age. After 8 years, signs of calcification appear in the gland, which are expressed in the deposition of the so-called "brain sand". According to Kitay and Altschule, the deposition of brain sand in the first decade of a person's life is observed from 0 to 5%, in the second - from 11 to 60%, and in the fifth it reaches 58-75%. Brain sand consists of an organic base permeated with carbonic and phosphate calcium and magnesium. Simultaneously with the age-related restructuring of the gland parenchyma, its vascular network also changes. The small-looped arterial network, rich in anastomoses, characteristic of the newborn's pineal gland, is replaced with age by longitudinal, weakly branching arteries. In an adult, the arteries of the pineal gland take the form of highways elongated along the length.

The process of involution of the pineal gland, which began at the age of 4-8, further progresses, however, individual cells of the parenchyma of the pineal gland remain until very old age.

Signs of secretory activity of pineal gland cells revealed during histological examination are found already in the second half of a person's embryonic life. In adolescence, despite a sharp decrease in the size of the pineal parenchyma, the secretory function of the main pineal cells does not stop.

Until now, it has not been fully studied, and it is now called a mysterious gland. In children, the pineal gland is relatively large than in adults, and produces hormones that affect the sexual cycle, lactation, carbohydrate and water-electrolyte metabolism. ,

The cellular elements of the gland are pinealocytes and glial cells (gliocytes).

The pineal gland performs a number of very important functions in the human body:

Glazing on the pituitary gland, suppressing its work

Stimulation of immunity

Prevents stress

Sleep regulation

Inhibition of sexual development in children

· A decrease in the secretion of growth hormone (growth hormone).

Pineal cells exert a direct inhibitory effect on the pituitary gland before puberty. In addition, they take part in almost all metabolic processes in the body.

This organ is closely connected with the nervous system: all light impulses that the eyes receive, before reaching the brain, travel through the pineal gland. Under the influence of light in the daytime, the pineal gland is suppressed, and in the dark, its work is activated and the secretion of the hormone melatonin begins. The epiphysis participates in the formation of circadian rhythms of sleep and wakefulness, rest and high emotional and physical recovery.

The hormone melatonin is a derivative of serotonin, which is a key biologically active substance of the circadian system, that is, the system responsible for the body's circadian rhythms.

The pineal gland is also responsible for immunity. With age, it atrophies, significantly decreasing in size. Atrophy of the pineal gland is also caused by exposure to fluoride, which was proved by the doctor Jennifer Luke, who found that excess fluoride causes early puberty, often provokes the formation of cancer, and also its large amount in the body can cause genetic abnormalities during fetal development during pregnancy ... Excessive use of fluoride can have detrimental effects on the body, causing DNA damage, tooth decay and loss, and obesity.

The pineal gland, being an organ of internal secretion, is directly involved in the metabolism of phosphorus, potassium, calcium and magnesium.

Pineal gland cells synthesize two main groups of active substances:

Indoles;

· Peptides.

All indoles are derivatives of the amino acid serotonin. This substance accumulates in the gland, and at night it is actively converted into melatonin (the main hormone of the pineal gland).

Serotonin and melatonin regulate the body's "biological clock". Hormones are derived from the amino acid tryptophan. Initially, serotonin is synthesized from tryptophan, and melatonin is formed from the latter. It is an antagonist of the melanocyte-stimulating hormone of the pituitary gland, produced at night, inhibits the secretion of gonadoliberin, thyroid hormones, adrenal hormones, growth hormone, sets the body to rest. Melatonin is released into the bloodstream, signaling to all cells in the body that night has come. Receptors for this hormone are found in almost all organs and tissues. In addition, melatonin can be converted to adrenoglomerulotropin. This pineal gland hormone affects the adrenal cortex, increasing the synthesis of aldosterone.

In boys, melatonin levels decline during puberty. In women, the highest level of melatonin is determined during menstruation, the lowest - during ovulation. Serotonin production predominates during the daytime. At the same time, sunlight switches the pineal gland from the formation of melatonin to the synthesis of serotonin, which leads to the awakening and wakefulness of the body (serotonin is an activator of many biological processes).

The effect of melatonin on the body is very diverse and manifests itself in the following functions:

· Regulation of sleep;

· Calming effect on the central nervous system;

· Lowering blood pressure;

· Hypoglycemic effect;

· Decrease in blood cholesterol levels;

· Immunostimulation;

· Antidepressant effect;

Retention of potassium in the body.

The pineal gland produces about 40 hormones of a peptide nature, of which the most studied are:

A hormone that regulates calcium metabolism;

The hormone arginine-vasotocin, which regulates the tone of the arteries and inhibits the secretion of follicle-stimulating hormone and luteinizing hormone by the pituitary gland.

It has been shown that pineal gland hormones suppress the development of malignant tumors. Light is the function of the pineal gland, and darkness stimulates it. The neural pathway was revealed: retina - retinohypothalamic tract - spinal cord - sympathetic ganglia - pineal gland.

In addition to melatonin, the inhibitory effect on sexual functions is also due to other hormones of the pineal gland - arginine-vasotocin, antigonadotropin.

Pineal adrenoglomerulotropin stimulates the formation of aldosterone in the adrenal glands.

Pinealocytes produce several dozen regulatory peptides. Of these, the most important are arginine-vasotocin, thyroliberin, luliberin and even thyrotropin.

The formation of oligopeptide hormones together with neuroamines (serotonin and melatonin) demonstrates that pinealocytes of the pineal gland belong to the APUD system.

The pineal gland hormones inhibit the bioelectric activity of the brain and neuropsychic activity, providing a hypnotic and calming effect.

The pineal gland peptides affect the immune system, metabolism and vascular tone.

Thymus, or thymus, gland, thymus, along with the red bone marrow, is the central organ of immunogenesis (see Fig. 44). In the thymus, stem cells coming here from the bone marrow with the blood flow, after going through a number of intermediate stages, ultimately turn into T-lymphocytes, which are responsible for the reactions of cellular immunity. In addition to the immunological function and the function of hematopoiesis, endocrine activity is inherent in the thymus. On this basis, this gland is considered as an organ of internal secretion.

Fig. 44. Thymus

The thymus consists of two lobes that are asymmetric in size: the right and left, connected by loose connective tissue. The thymus is located in the upper part of the anterior mediastinum, behind the handle of the sternum. By the time the child is born, the weight of the gland is 15 g. The size and weight of the thymus increases as the child grows up to the onset of puberty. During its maximum development (10-15 years), the mass of the thymus reaches an average of 37.5 g, its length at this time is 7.5-16 cm.From the age of 25, age-related involution of the thymus begins - a gradual decrease in the glandular tissue with replacement her fatty tissue.

Thymus functions

1. Immune. It lies in the fact that the thymus plays a key role in the maturation of immunocompetent cells, and also determines the safety and correct course of various immune responses. The thymus gland primarily determines the differentiation of T-lymphocytes, and also stimulates their release from the bone marrow. In the thymus, thymalin, thymosin, thymopoietin, thymic humoral factor and insulin-like growth factor-1 are synthesized, these are polypeptides that are chemical stimulants of immune processes.

2. Neuroendocrine. The implementation of this function is ensured by the fact that the thymus takes part in the formation of certain biologically active substances.

All substances that are formed by the thymus have a different effect on the child's body. Some act locally, that is, in the place of formation, while others - systemically, spreading with the blood stream. Therefore, biologically active substances of the thymus gland can be divided into several classes. One of the classes is similar to hormones that are produced in the endocrine organs. In the thymus, antidiuretic hormone, oxytocin, somatostatin are synthesized. Currently, the endocrine function of the thymus is not well understood.

Thymus hormones and their secretion are regulated by glucocorticoids, that is, hormones of the adrenal cortex. In addition, interferons, lymphokines and interleukins produced by other cells of the immune system are responsible for the function of this organ.

Pancreas refers to glands with mixed secretion (see Fig. 45). In it, not only pancreatic digestive juice is formed, but also hormones are produced: insulin, glucagon, lipocaine and others.

In a newborn, it is located deep in the abdominal cavity, at the level of the X-th thoracic vertebra, its length is 5-6 cm. In young and older children, the pancreas is at the level of the I-th lumbar vertebra. The gland grows most intensively in the first 3 years and during puberty. At birth and in the first months of life, it is insufficiently differentiated, abundantly vascularized and poor in connective tissue. The head of the pancreas is most developed in a newborn. At an early age, the surface of the pancreas is smooth, and by 10–12 years, tuberosity appears, due to the separation of the boundaries of the lobules.

Fig. 45. Pancreas

The endocrine part of the pancreas is represented by groups of epithelial cells that form a peculiar form of pancreatic islets (P. Langerhans islets), separated from the rest of the exocrine part of the gland by thin layers of loose fibrous connective tissue.

Pancreatic islets are found in all parts of the pancreas, but most of them in the tail of the gland. The size of the islets is from 0.1 to 0.3 mm, the number is 1-2 million, and their total mass does not exceed 1% of the mass of the pancreas. The islets are composed of endocrine cells - several types of insulocytes. Approximately 70% of all cells are beta cells that produce insulin, the rest of the cells (about 20%) are alpha cells that produce glucagon. delta cells (5-8%) secrete somatostatin. It delays the release of insulin and glucagon by B- and A-cells and inhibits the synthesis of enzymes by the pancreatic tissue.

D-cells (0.5%) secrete a vasoactive intestinal polypeptide, which lowers blood pressure, stimulates the secretion of juice and hormones by the pancreas. PP cells (2-5%) produce a polypeptide that stimulates the secretion of gastric and pancreatic juice. The epithelium of the small excretory ducts secretes lipocaine.

To assess the activity of the islet apparatus of the gland, it is necessary to remember about the close mutual influence on the amount of blood sugar by the function of the pituitary gland, adrenal glands, insular apparatus and liver. In addition, the sugar content is directly related to the secretion of glucagon by the islet cells of the gland, which is an insulin antagonist. Glucagon promotes the release of glucose into the blood from liver glycogen stores. The secretion of these hormones and interactions are regulated by fluctuations in blood sugar.

The main hormone in the pancreas is insulin, which has the following functions:

1) promotes the synthesis of glycogen and its accumulation in the liver and muscles;

2) increases the permeability of cell membranes for glucose and promotes its intensive oxidation in tissues;

3) causes hypoglycemia, i.e. a decrease in the level of glucose in the blood and, as a consequence, an insufficient supply of glucose into the cells of the central nervous system, on the permeability of which insulin does not act;

4) normalizes fat metabolism and reduces ketonuria;

5) reduces protein catabolism and stimulates the synthesis of proteins from amino acids;

6) retains water in tissues

7) reduces the formation of carbohydrates from protein and fat;

8) promotes the assimilation of substances split during digestion, their distribution in the body after entering the bloodstream. It is thanks to insulin that carbohydrates, amino acids and some components of fats can penetrate through the cell wall from the blood into every cell of the body. Without insulin, with a defect in the hormone molecule or cell receptor, nutrients dissolved in the blood remain in its composition and have a toxic effect on the body.

The production and secretion of insulin is regulated by blood glucose levels with the involvement of the autonomic nervous system and the hypothalamus. An increase in blood glucose after taking large amounts of it, with strenuous physical work, emotions, etc. increases insulin secretion. Conversely, lowering blood glucose levels inhibits insulin secretion. Excitation of the vagus nerves stimulates the formation and release of insulin, sympathetic - inhibits this process.

The concentration of insulin in the blood depends not only on the intensity of its formation, but also on the rate of its destruction. Insulin is destroyed by the enzyme insulinase, which is found in the liver and skeletal muscles. The most active is liver insulinase. With a single flow of blood through the liver, up to 50% of the insulin contained in it can be destroyed.

With insufficient intrasecretory function of the pancreas, a serious disease is observed - diabetes, or sugar diabetes. The main manifestations of this disease are: hyperglycemia (up to 44.4 mmol / L), glucosuria (up to 5% sugar in urine), polyuria (profuse urination: from 3-4 liters to 8-9 liters per day), polydipsia (increased thirst), polyphagia (increased appetite), weight loss (weight loss), ketonuria. In severe cases, a diabetic coma (loss of consciousness) develops.

The second hormone of the pancreas, glucagon, by its action is an insulin antagonist and performs the following functions:

1) breaks down glycogen in the liver and muscles to glucose;

2) causes hyperglycemia;

3) stimulates the breakdown of fat in adipose tissue;

4) increases the contractile function of the myocardium without affecting its excitability.

The formation of glucagon in alpha cells is influenced by the amount of glucose in the blood. With an increase in blood glucose, the secretion of glucagon decreases (inhibited), with a decrease, it increases. The hormone of the adenohypophysis - somatotropin increases the activity of A-cells, stimulating the formation of glucagon.

The third hormone, lipocaine, is formed in the cells of the epithelium of the excretory ducts of the pancreas, promotes the utilization of fats due to the formation of lipids and increased oxidation of higher fatty acids in the liver, which prevents fatty degeneration of the liver. It is allocated by the insular apparatus of the gland.

Adrenal glandsare vital, essential for the body. Removal of both adrenal glands leads to death due to the loss of large amounts of sodium in the urine and a decrease in sodium levels in the blood and tissues (due to the lack of aldosterone).

The adrenal gland is a paired organ located in the retroperitoneal space just above the upper end of the corresponding kidney (see Fig. 46). The right adrenal gland has the shape of a triangle, the left one is crescent-shaped (resembles a crescent). Located at the level of the XI-XII thoracic vertebrae. The right adrenal gland, like the kidney, lies somewhat lower than the left.

Figure: 46. \u200b\u200bAdrenal glands

At birth, the mass of one adrenal gland in a child reaches 7 g, their size is 1/3 the size of the kidney. In a newborn, the adrenal cortex, like in a fetus, consists of 2 zones - fetal and definitive (permanent), with the bulk of the gland being the fetal. The definitive zone functions in the same way as in an adult. The bundle zone is narrow, indistinctly formed, there is no reticular zone yet.

During the first 3 months of life, the mass of the adrenal gland decreases by half, to an average of 3.4 g, mainly due to the thinning and restructuring of the cortex; after a year, it begins to increase again. By the age of one year, the fetal zone completely disappears, and in the definitive cortex, the glomerular, fascicular and reticular zones are already distinguishable.

By the age of 3, the differentiation of the adrenal cortex is completed. The formation of zones of the cortical substance lasts up to 11-14 years, by this period the ratio of the width of the glomerular, fascicular and reticular zones is 1: 1: 1. By the age of 8, there is an increased growth of the brain substance.

Its final formation ends by 10-12 years. The mass of the adrenal glands noticeably increases in the pre- and pubertal periods and by the age of 20 it increases by 1.5 times in comparison with their mass in a newborn, reaching the indicators characteristic of an adult.

The mass of one adrenal gland in an adult is about 12-13g. The length of the adrenal gland is 40-60 mm, the height (width) is 20-30 mm, the thickness (anteroposterior size) is 2-8 mm. Outside, the adrenal gland is covered with a fibrous capsule, which radiates numerous connective tissue trabeculae deep into the organ and dividing the gland into two layers: the outer layer is the cortex (cortex) and the inner layer is the medulla. The cortex accounts for about 80% of the mass and volume of the adrenal gland. In the adrenal cortex, 3 zones are distinguished: outer - glomerular, middle - bundle and inner - reticular.

The morphological features of the zones are reduced to the distribution of glandular cells, connective tissue and blood vessels, which is peculiar for each zone. The listed zones are functionally isolated due to the fact that the cells of each of them produce hormones that differ from each other not only in chemical composition, but also in physiological action.

The glomerular zone - the thinnest layer of the cortex, adjacent to the adrenal capsule, consists of small epithelial cells, forming cords in the form of tangles. The glomerular zone produces mineralocorticoids: aldosterone, deoxycorticosterone.

The bundle zone is a large part of the cortex, very rich in lipids, cholesterol, and vitamin C. When stimulated with ACTH, cholesterol is spent on the formation of corticosteroids. This zone contains larger glandular cells lying in parallel strands (bundles). The bundle zone produces glucocorticoids: hydrocortisone, cortisone, corticosterone.

The reticular zone is adjacent to the medulla. It contains small glandular cells arranged in a network. The reticular zone forms sex hormones: androgens, estrogens and a small amount of progesterone.

The adrenal medulla is located in the center of the gland. It is formed by large chromaffin cells, stained with chromium salts in a yellowish-brown color. There are two types of these cells: epinephrocytes make up the bulk and produce catecholamine - adrenaline; norepinephrocytes, scattered in the medulla in small groups, produce another catecholamine, norepinephrine.

A. Physiological significance of glucocorticoids - hydrocortisone, cortisone, corticosterone:

1) stimulate adaptation and increase the body's resistance to stress;

2) affect the metabolism of carbohydrates, proteins, fats;

3) delay the utilization of glucose in tissues;

4) promote the formation of glucose from proteins (glyconeogenesis);

5) cause the breakdown (catabolism) of tissue protein and delay the formation of granulations;

6) inhibit the development of inflammatory processes (anti-inflammatory effect);

7) suppress the synthesis of antibodies;

8) suppress the activity of the pituitary gland, especially the secretion of ACTH.

B. Physiological significance of mineralocorticoids - aldosterone, deoxycorticosterone:

1) preserve sodium in the body, as they enhance the reabsorption of sodium in the renal tubules;

2) remove potassium from the body, as they reduce the reabsorption of potassium in the renal tubules;

3) promote the development of inflammatory reactions, since they increase the permeability of capillaries and serous membranes (pro-inflammatory effect);

4) increase the osmotic pressure of blood and tissue fluid (due to an increase in sodium ions in them);

5) increase vascular tone, increasing blood pressure.

With a lack of mineralocorticoids, the body loses such a large amount of sodium that it leads to changes in the internal environment incompatible with life. Therefore, mineralocorticoids are figuratively called life-saving hormones.

B. Physiological significance of sex hormones - androgens, estrogens, progesterone:

1) stimulate the development of the skeleton, muscles, genitals in childhood, when the intrasecretory function of the gonads is still insufficient;

2) cause the development of secondary sexual characteristics;

3) provide the normalization of sexual functions;

4) stimulate anabolism and protein synthesis in the body.

With insufficient function of the adrenal cortex, the so-called bronze, or Addison's, disease develops (see Fig. 47).

The main signs of this disease are: weakness (muscle weakness), weight loss (weight loss), hyperpigmentation of the skin and mucous membranes (bronze coloration), arterial hypotension.

With hyperfunction of the adrenal cortex (for example, with a tumor), there is a predominance of the synthesis of sex hormones over the production of gluco- and mineralocorticoids (a sharp change in secondary sexual characteristics).

Figure: 47. Addison's disease

The regulation of glucocorticoid formation is carried out by corticotropin (ACTH) of the anterior pituitary gland and corticoliberin of the hypothalamus. Corticotropin stimulates the production of glucocorticoids, and with an excess in the blood of the latter, the synthesis of corticotropin (ACTH) in the anterior pituitary gland is inhibited. Corticoliberin (corticotropin-releasing hormone) enhances the formation and release of corticotropin through the general circulatory system of the hypothalamus and pituitary gland. Given the close functional relationship of the hypothalamus, pituitary and adrenal glands, we can therefore talk about a single hypothalamic-pituitary-adrenal system.

The formation of mineralocorticoids is influenced by the concentration of sodium and potassium ions in the body. With an excess of sodium and a lack of potassium in the body, the secretion of aldosterone decreases, which leads to increased excretion of sodium in the urine. With a lack of sodium and an excess of potassium in the body, the secretion of aldosterone in the adrenal cortex increases, as a result of which the excretion of sodium in the urine decreases, and the excretion of potassium increases.

D. Physiological significance of adrenal medulla hormones: adrenaline and norepinephrine.

Adrenaline and norepinephrine are combined under the name "catechol-mines", i.e. derivatives of pyrocatechol (organic compounds of the phenol class), actively participating as hormones and mediators in physiological and biochemical processes in the human body.

Epinephrine and norepinephrine cause:

1) strengthening and lengthening the effect of the influence of the sympathetic nervous

2) hypertension, with the exception of the vessels of the brain, heart, lungs and working skeletal muscles;

3) cleavage of glycogen in the liver and muscles and hyperglycemia;

4) stimulation of the heart;

5) increasing the energy and performance of skeletal muscles;

6) dilation of the pupils and bronchi;

7) the appearance of the so-called goose bumps (straightening of skin hair) due to the contraction of smooth muscles of the skin that raise the hair (pilomotors);

8) inhibition of secretion and motility of the gastrointestinal tract.

In general, adrenaline and norepinephrine are important in mobilizing reserve capacities and body resources. Therefore, they are reasonably called anxiety hormones or "emergency hormones".

The secretory function of the adrenal medulla is controlled by the posterior part of the hypothalamus, where the higher subcortical autonomic centers of sympathetic innervation are located. When the sympathetic splanchnic nerves are irritated, the adrenaline release from the adrenal glands increases, and when they are cut, it decreases. Irritation of the nuclei of the posterior part of the hypothalamus also increases the release of adrenaline from the adrenal glands and increases its content in the blood. The release of adrenaline from the adrenal glands under various influences on the body is regulated by the level of sugar in the blood. In hypoglycemia, the reflex adrenaline rush increases. Under the influence of adrenaline, an increased formation of glucocorticoids occurs in the adrenal cortex. Thus, adrenaline humorally supports the shifts caused by excitation of the sympathetic nervous system, i.e. Supports long-term restructuring of functions required in emergency situations. Consequently, adrenaline is figuratively called the "liquid sympathetic nervous system".

Sex glands : testicle in men (see Fig. 49) and ovary in women (see Fig. 48) are glands with mixed function.

Fig. 48. Ovaries Fig. 49 Testicle

The ovaries are paired glands, located in the pelvic cavity, approximately 2 × 2 × 3 cm in size. They consist of a dense cortex outside and a soft brain inside.

The cortical substance is predominant in the ovaries. Eggs mature in the cortex. Sex cells are formed in a female fetus at 5 months of intrauterine development once and for all. From this moment on, not a single reproductive cell is formed, they only die. A newborn girl has about a million oocytes (sex cells) in her ovaries; by the time of puberty, only 300 thousand of them remain. During life, only 300-400 of them will turn into mature eggs, and only a few will be fertilized. The rest will die.

The testicles are paired glands located in the musculocutaneous saccular formation - the scrotum. They are formed in the abdominal cavity and by the time the child is born or by the end of the 1st year of life (possibly even during the first seven years) they descend into the scrotum through the inguinal canal.

In an adult man, the size of the testicles is on average 4X 3 cm, their weight is 20-30 g, in 8-year-old children - 0.8 g, in 15-year-old adolescents - 7-10 g. The testicle is divided into 200-300 lobules by many partitions, each of which is filled with very thin convoluted seminiferous tubules (tubes). In them, from the period of puberty to a very old age, male sex cells - spermatozoa - are continuously formed and matured.

Due to the exocrine function of these glands, male and female reproductive cells are formed - spermatozoa and eggs. The intrasecretory function is manifested in the secretion of sex hormones that enter the bloodstream.

There are two groups of sex hormones: male - androgens (Greek andros - male) and female - estrogens (Greek oistrum - estrus). Both are formed from cholesterol and deoxycorticosterone in both male and female gonads, but not in equal amounts. The endocrine function in the testicle is possessed by the interstitium, represented by glandular cells - interstitial endocrinocytes of the testis (F. Leydig's cells). These cells are located in the loose fibrous connective tissue between the convoluted tubules, next to the blood and lymphatic capillaries. Testicular interstitial endocrinocytes secrete male sex hormones: testosterone and androsterone.

Physiological significance of androgens - testosterone and androsterone:

1) stimulate the development of secondary sexual characteristics;

2) affect sexual function and reproduction;

3) have a great effect on the metabolism: they increase the formation of protein, especially in the muscles, reduce the fat content in the body, increase the basal metabolism;

4) affect the functional state of the central nervous system, higher nervous activity and behavior.

Female sex hormones are formed: estrogens - in the granular layer of maturing follicles, as well as in the cells of the ovarian interstitium, progesterone - in the corpus luteum of the ovary at the site of the burst follicle.

Physiological significance of estrogens:

1) stimulate the growth of genitals and the development of secondary sexual characteristics;

2) promote the manifestation of sexual reflexes;

3) cause hypertrophy of the uterine mucosa in the first half of the menstrual cycle;

4) during pregnancy - stimulate the growth of the uterus.

Physiological significance of progesterone:

1) ensures the implantation and development of the fetus in the uterus during pregnancy;

2) inhibits the production of estrogen;

3) inhibits the contraction of the muscles of the pregnant uterus and reduces its sensitivity to oxytocin;

4) delays ovulation by inhibiting the formation of the hormone of the anterior pituitary gland - lutropin.

The formation of sex hormones in the gonads is under the control of the gonadotropic hormones of the anterior pituitary gland: follitropin and lutropin. The function of the adenohypophysis is controlled by the hypothalamus, which secretes the pituitary hormone - gonadoliberin, which can increase or inhibit the release of gonadotropins by the pituitary gland.

Removal (castration) of the gonads at different periods of life leads to different effects. In very young organisms, it has a significant effect on the formation and development of the animal, causing a stop in the growth and development of the genitals, their atrophy. Animals of both sexes become very similar to each other, i.e. as a result of castration, there is a complete violation of the sexual differentiation of animals. If castration is performed in adult animals, the resulting changes are limited mainly to the genitals. Removal of the gonads significantly changes the metabolism, the nature of the accumulation and distribution of fatty deposits in the body. Transplantation of the gonads to castrated animals leads to the practical restoration of many impaired body functions.

Male hypogenitalism (eunuchoidism), characterized by underdevelopment of the genitals and secondary sexual characteristics, is the result of various lesions of the testes (testicles) or develops as a secondary disease with damage to the pituitary gland (loss of its gonadotropic function).

In women, with a low content of female sex hormones in the body as a result of damage to the pituitary gland (loss of its gonadotropic function) or insufficiency of the ovaries themselves, female hypogenitalism develops, characterized by insufficient development of the ovaries, uterus and secondary sexual characteristics.

Sexual development

The process of puberty takes place under the control of the central nervous system and endocrine glands. The leading role in it is played by the hypothalamic-pituitary system. The hypothalamus, being the highest autonomic center of the nervous system, controls the state of the pituitary gland, which, in turn, controls the activity of all endocrine glands. The neurons of the hypothalamus secrete neurohormones (releasing factors), which, entering the pituitary gland, enhance (liberins) or inhibit (statins) the biosynthesis and release of triple hormones of the pituitary gland. Tropic hormones of the pituitary gland, in turn, regulate the activity of a number of endocrine glands (thyroid, adrenal, reproductive), which, to the extent of their activity, change the state of the internal environment of the body and affect behavior.

An increase in the activity of the hypothalamus in the initial stages of puberty consists in specific connections of the hypothalamus with other endocrine glands. Hormones secreted by the peripheral endocrine glands have an inhibitory effect on the highest link of the endocrine system. This is an example of the so-called feedback, which plays an important role in the functioning of the endocrine system. It provides self-regulation of the endocrine glands. At the beginning of puberty, when the gonads are not yet developed, there are no conditions for their reverse inhibitory effects on the hypothalamic-pituitary system, therefore the own activity of this system is very high. This causes an increased release of tropic hormones from the pituitary gland, which have a stimulating effect on growth processes (somatotropin) and the development of the gonads (gonadotropins).

At the same time, the increased activity of the hypothalamus cannot but affect the relationship between the subcortical structures and the cerebral cortex.

Puberty is a stage process, therefore age-related changes in the state of the nervous system of adolescents develop gradually and have a certain specificity due to the dynamics of puberty. These changes are reflected in the psyche and behavior.

There are several periodizations of puberty, mainly based on the description of changes in the genitals and secondary sexual characteristics. In both boys and girls, there are five stages of puberty.

Stage one - childhood (infantilism); it is characterized by a slow, almost imperceptible development of the reproductive system; the leading role belongs to thyroid hormones and growth hormones of the pituitary gland. The genitals develop slowly during this period, there are no secondary sexual characteristics. This stage ends at 8-10 years old for girls and 10-13 years old for boys.

Stage two - pituitary - marks the beginning of puberty. The changes that occur at this stage are due to the activation of the pituitary gland: the secretion of pituitary hormones (somatotropins and follitropin) increases, which affect the growth rate and the appearance of the initial signs of puberty. The stage ends, as a rule, in girls at 9-12 years old, in boys at 12-14 years old.

Third stage - the stage of activation of the sex glands (stage of activation of the gonads). The gonadotropic hormones of the pituitary gland stimulate the sex glands, which begin to produce steroid hormones (androgens and estrogens). At the same time, the development of the genitals and secondary sexual characteristics continues.

Fourth stage - maximum steroidogenesis - begins at 10-13 years old in girls and 12-16 years old in boys. At this stage, under the influence of gonadotropic hormones, the sex glands (testes and ovaries), producing male (androgens) and female (estrogens) hormones, reach the greatest activity. The increase in secondary sexual characteristics continues, and some of them reach their definitive form at this stage. At the end of this stage, girls begin their period.

Fifth stage - the final formation of the reproductive system - begins at the age of 11-14 for girls and 15-17 years for boys. Physiologically, this period is characterized by the establishment of a balanced feedback between the pituitary hormones and the peripheral glands. Secondary sexual characteristics are already fully expressed. The girls have a regular menstrual cycle. In young men, the hairy skin of the face and lower abdomen ends. The age of the end of puberty in girls is 15-16 years old, in boys - 17-18 years old. However, large individual differences are possible here: fluctuations in timing can be up to 2-3 years, especially among girls.

Similar information.

Changes on the part of the endocrine glands are heterochronous, that is, at different times. So the function of the pituitary gland is preserved until old age.

In the thyroid gland, there are significant changes in its structure. The mass of the gland decreases due to the replacement of part of the glandular tissue with fatty tissue. The rate of accumulation of iodine in the gland decreases. The consumption of oxygen by the glandular tissue decreases, which leads to a decrease in the synthesis of thyroid hormones, at the same time the sensitivity of tissues and organs to humoral factors increases, including to thyroid hormones.

Therefore, in the body, self-regulation processes are maintained at a high level for a long time.

The female sex glands are the ovaries.

The size and shape of the ovaries changes with age. They reach their maximum mass by the age of 30. After 40 years, there is a progressive decrease in the mass of the ovaries, they change their shape, undergo atrophy and fibrosis.

Despite the changes taking place, the ovaries retain their ability to produce estrogen for a long time. Due to estrogens, proliferative processes in the mucous membrane of the uterus and vagina are supported, the shape of the mammary glands is preserved, and secondary sexual characteristics are preserved.

With the onset of menopause, estrogen production drops sharply, and this leads to a regression of secondary sexual characteristics. Against this background, the rapid development of atherosclerosis, osteoporosis, deforming osteoarthritis is possible.

The male sex glands are the testicles.

Age-related changes in the male genital glands occur at a later age than in women and flow at a slower pace. Male sex glands reach the greatest mass by the age of 25 - 30, later they slightly decrease in mass. Age-related changes occurring in them lead to a decrease in spermatogenesis, but this is purely individual. Gerontologists noted that even in very old people, normal, active spermatozoa are found in the semen.

With age, the testicles show obliteration of the seminiferous tubules. The number of Leydig cells responsible for the production of androgens decreases. Therefore, with aging of the genital glands in men, the extinction of secondary sexual characteristics is noted, gynecomastia appears, the timbre of the voice changes, the development of female obesity is possible, the growth of a mustache and beard slows down. Perhaps the development of mental weakness and a decrease in physical strength.

Factors accelerating the aging of the endocrine system:

Smoking,

Alcoholism,

substance abuse,

surgical interventions,

viral infections

use of medicines