The hypothalamus secretes two oppositely acting hormones - releasing factor and somatostatin, which are sent to the adenopituitary gland and regulate the production and release of growth hormone. It is still unknown what stimulates the release of growth hormone from the pituitary gland more strongly - an increase in the concentration of releasing factor or a decrease in the content of somatostatin. Growth hormone is not secreted evenly, but sporadically, 3-4 times during the day. Increased secretion of growth hormone occurs under the influence of fasting, severe muscle work, and also during deep sleep: it’s not without reason, apparently, folk tradition claims that children grow at night. With age, the secretion of growth hormone decreases, but nevertheless does not stop throughout life. After all, in an adult, growth processes continue, only they no longer lead to an increase in the mass and number of cells, but ensure the replacement of obsolete, spent cells with new ones.
Growth hormone released by the pituitary gland produces two different effects on the cells of the body. The first - direct - effect is that the breakdown of previously accumulated reserves of carbohydrates and fats intensifies in the cells, their mobilization for the needs of energy and plastic metabolism. The second - indirect - action is carried out with the participation of the liver. In its cells, under the influence of growth hormone, mediator substances are produced - somatomedins, which already affect all cells of the body. Under the influence of somatomedins, bone growth, protein synthesis and cell division are enhanced, i.e., the very processes that are commonly called “growth” occur. At the same time, molecules of fatty acids and carbohydrates, released due to the direct action of growth hormone, take part in the processes of protein synthesis and cell division.
If the production of growth hormone is reduced, the child does not grow and becomes dwarf. At the same time, he maintains a normal physique. Growth may also stop prematurely due to disturbances in the synthesis of somatomedins (it is believed that this substance, for genetic reasons, is not produced in the liver of pygmies, who have the adult height of a 7-10 year old child). On the contrary, hypersecretion of growth hormone in children (for example, due to the development of a benign pituitary tumor) can lead to gigantism. If hypersecretion begins after the ossification of the cartilaginous areas of the bones has already been completed under the influence of sex hormones, acromegaly- limbs, hands and feet, nose, chin and other extremities of the body, as well as the tongue and digestive organs, lengthen disproportionately. Dysfunction of endocrine regulation in patients with acromegaly often leads to various diseases, including the development diabetes mellitus. Timely applied hormonal therapy or surgical intervention can avoid the most dangerous development of the disease.
Growth hormone begins to be synthesized in the human pituitary gland at the 12th week of intrauterine life, and after the 30th week its concentration in the fetal blood becomes 40 times higher than in an adult. By the time of birth, the concentration of growth hormone drops by about 10 times, but still remains extremely high. During the period from 2 to 7 years, the content of growth hormone in the blood of children remains at approximately constant levels, which are 2–3 times higher than the level of adults. It is significant that during this same period the most rapid growth processes are completed before the onset of puberty. Then comes a period of significant decrease in hormone levels - and growth is inhibited. A new increase in the level of growth hormone in boys is observed after 13 years, and its maximum is observed at 15 years, i.e., just at the moment of the most intense increase in body size in adolescents. By the age of 20, the level of growth hormone in the blood is established at typical adult levels.
With the onset of puberty, sex hormones that stimulate protein anabolism are actively involved in the regulation of growth processes. It is under the influence of androgens that the somatic transformation of a boy into a man occurs, since under the influence of this hormone the growth of bone and muscle tissue is accelerated. An increase in the concentration of androgens during puberty causes an abrupt increase in the linear dimensions of the body - it occurs pubertal growth spurt. However, following this, the same increased content of androgens leads to ossification of the growth zones in long bones, as a result of which their further growth stops. In the case of premature puberty, body growth in length may begin excessively early, but it will end early, and as a result the boy will remain “undersized.”
Androgens also stimulate increased growth of the muscles and cartilaginous parts of the larynx, as a result of which boys’ voices “break” and become much lower. The anabolic effect of androgens extends to all skeletal muscles of the body, due to which the muscles in men are much more developed than in women. Female estrogens have a less pronounced anabolic effect than androgens. For this reason, in girls during puberty, the increase in muscles and body length is less, and the pubertal growth spurt is less pronounced than in boys.
Although most endocrine glands begin to function in utero, the first serious test for the entire system of biological regulation of the body is the moment of childbirth. Birth stress is an important trigger for numerous processes of adaptation of the body to new conditions of existence. Any disturbances and deviations in the functioning of the regulatory neuroendocrine systems that occur during the birth of a child can have a serious impact on the child’s health throughout the rest of his life.
The first - urgent - reaction of the fetal neuroendocrine system at the time of birth is aimed at activating metabolism and external respiration, which did not function at all in utero. The first breath of a child is the most important criterion for a live birth, but in itself it is a consequence of complex nervous, hormonal and metabolic influences. In umbilical cord blood there is a very high concentration of catecholamines - adrenaline and norepinephrine, hormones of “urgent” adaptation. They not only stimulate energy metabolism and the breakdown of fats and polysaccharides in cells, but also inhibit the formation of mucus in lung tissue, and also stimulate the respiratory center located in the brain stem. In the first hours after birth, the activity of the thyroid gland rapidly increases, the hormones of which also stimulate metabolic processes. All these hormonal releases are carried out under the control of the pituitary gland and hypothalamus. Children born by caesarean section and therefore not exposed to the natural stress of childbirth have significantly lower levels of catecholamines and thyroid hormones in the blood, which negatively affects their lung function during the first 24 hours of life. As a result, their brain suffers from some lack of oxygen, and this may have some effect later.
Hormonal regulation of growth
The hypothalamus secretes two oppositely acting hormones - releasing factor and somatostatin, which are sent to the adenopituitary gland and regulate the production and release of growth hormone. It is still unknown what stimulates the release of growth hormone from the pituitary gland more strongly - an increase in the concentration of releasing factor or a decrease in the content of somatostatin. Growth hormone is not secreted evenly, but sporadically, 3-4 times during the day. Increased secretion of growth hormone occurs under the influence of fasting, heavy muscular work, and also during deep sleep: it is not without reason that folk tradition claims that children grow at night. With age, the secretion of growth hormone decreases, but nevertheless does not stop throughout life. After all, in an adult, growth processes continue, only they no longer lead to an increase in the mass and number of cells, but ensure the replacement of obsolete, spent cells with new ones.
Growth hormone released by the pituitary gland produces two different effects on the cells of the body. The first - direct - effect is that the breakdown of previously accumulated reserves of carbohydrates and fats intensifies in the cells, their mobilization for the needs of energy and plastic metabolism. The second - indirect - action is carried out with the participation of the liver. In its cells, under the influence of growth hormone, mediator substances are produced - somatomedins, which already affect all cells of the body. Under the influence of somatomedins, bone growth, protein synthesis and cell division are enhanced, i.e. the very processes that are commonly called “growth” take place. At the same time, molecules of fatty acids and carbohydrates, released due to the direct action of growth hormone, take part in the processes of protein synthesis and cell division.
If the production of growth hormone is reduced, the child does not grow and becomes a dwarf. At the same time, he maintains a normal physique. Growth may also stop prematurely due to disturbances in the synthesis of somatomedins (it is believed that this substance, for genetic reasons, is not produced in the liver of pygmies, who have the adult height of a 7-10 year old child). On the contrary, hypersecretion of growth hormone in children (for example, due to the development of a benign pituitary tumor) can lead to gigantism. If hypersecretion begins after the ossification of the cartilaginous areas of the bones has already been completed under the influence of sex hormones, acromegaly- limbs, hands and feet, nose, chin and other extremities of the body, as well as the tongue and digestive organs, lengthen disproportionately. Dysfunction of endocrine regulation in patients with acromegaly often leads to various metabolic diseases, including the development of diabetes mellitus. Timely applied hormonal therapy or surgical intervention allow you to avoid the most dangerous development of the disease.
Growth hormone begins to be synthesized in the human pituitary gland at the 12th week of intrauterine life, and after the 30th week its concentration in the fetal blood becomes 40 times higher than in an adult. By the time of birth, the concentration of growth hormone drops by about 10 times, but still remains extremely high. In the period from 2 to 7 years, the content of growth hormone in the blood of children remains at approximately a constant level, which is 2-3 times higher than the level of adults. It is significant that during this same period the most rapid growth processes are completed before the onset of puberty. Then comes a period of significant decrease in hormone levels - and growth is inhibited. A new increase in the level of growth hormone in boys is observed after 13 years, and its maximum is observed at 15 years, i.e. just at the moment of the most intense increase in body size in adolescents. By the age of 20, the level of growth hormone in the blood is established at typical adult levels.
With the onset of puberty, sex hormones that stimulate protein anabolism are actively involved in the regulation of growth processes. It is under the influence of androgens that the somatic transformation of a boy into a man occurs, since under the influence of this hormone the growth of bone and muscle tissue is accelerated. An increase in the concentration of androgens during puberty causes an abrupt increase in the linear dimensions of the body - a pubertal growth spurt occurs. However, following this, the same increased content of androgens leads to ossification of the growth zones in long bones, as a result of which their further growth stops. In the case of premature puberty, body growth in length may begin excessively early, but it will end early, and as a result the boy will remain “undersized.”
Androgens also stimulate increased growth of the muscles and cartilaginous parts of the larynx, as a result of which boys’ voices “break” and become much lower. The anabolic effect of androgens extends to all skeletal muscles of the body, due to which the muscles in men are much more developed than in women. Female estrogens have a less pronounced anabolic effect than androgens. For this reason, in girls during puberty, the increase in muscles and body length is less, and the pubertal growth spurt is less pronounced than in boys.
To the hormones that enable and provide physical, mental and sexual development, include growth hormone (GH), which is produced by the anterior pituitary gland, as well as thyroid hormones - thyroxine and triiodothyronine, pancreatic hormone - insulin, and sex hormones (Fig. 6.9).
Genetic factors play an important role. Nutrition must be balanced: starvation, diseases accompanied by protein catabolism lead to growth retardation in children.
Growth is uneven. The first peak in growth rate occurs in early childhood, the second during puberty. This is due to the simultaneous action of growth hormone, estrogens and androgens. The cessation of growth is associated with the closure of the epiphyseal growth plates under the influence of estrogens and androgens.
The role of growth hormone (GH) in the regulation of growth and physical development
Growth hormone is secreted by the anterior pituitary gland (adenohypophysis). According to its chemical structure, it is a polypeptide consisting of 191 amino acids. Growth hormone is species specific.
RICE. 6.9.
The synthesis and secretion of GH are carried out under the control of the hormones of the hypothalamus - growth hormone releasing factor (GHR), which stimulates these processes, and somatostatin (SS), which, on the contrary, inhibits the synthesis and secretion of GH. Hypothalamic hormones enter the adenohypophysis with the blood of the portal vessels.
The concentration of the hormone in the blood is higher in children and at a young age (before puberty), less in older age. The normal concentration of growth hormone in an adult is 2-6 ng/ml, in children - 5-8 ng/ml.
There is a daily allowance (circadian) biological rhythm of hormone secretion - secretion has a pulsating nature, increases at night: peak secretion is reached 1-2 hours after falling asleep and decreases during the day.
The secretion of growth hormone is affected a large number of factors. They can be roughly divided into stimulating and inhibitory. Stimulants include:
1 Fasting, especially protein fasting, and a decrease in the amount of free fatty acids in the blood, which leads to a significant decrease in the main substrates necessary to replenish the body’s energy.
2 Increase in the blood concentration of certain amino acids: arginine, leucine, lysine, tryptophan and 5-hydroxytryptophan.
3 Stress factors accompanied by increased physical activity, negative emotions and stimulation of the sympathoadrenal system.
4 Biologically active substances: insulin, estrogens, opiates (enkephalins and endorphins), testosterone.
Secretion is inhibited by: increased concentrations of glucose and free fatty acids in the blood; obesity and the aging process; hormones cortisone, progesterone, Somatomedin and exogenous growth hormone.
Regulation of GH secretion carried out by a control loop with a negative feedback channel (Fig. 6.10).
When growth hormone enters the blood, it binds to receptors on the membranes of target cells in the liver, where the hormones are produced Somatomedin(insulin-like growth factor - IGF), which also regulate the secretion of growth hormone through a negative feedback loop mechanism.
Somatomedin (IGF-I), firstly, is carried into the hypothalamus by the bloodstream and stimulates the synthesis of somatostatin, which inhibits the release of growth hormone by the pituitary gland; secondly, Somatomedin is directly carried by the bloodstream into the pituitary gland, where it also suppresses the secretion of growth hormone.
The effect of growth hormone on target cells occurs indirectly through Somatomedin (IGF-I) or directly.
For mammals, in which it is very difficult to experimentally disentangle growth and differentiation, a lot of data have been obtained regarding aging, including for very long-lived species. For amphibians, which have clear metamorphosis and in which growth and differentiation can be separated relatively easily, there is still no direct evidence regarding aging. It is difficult to establish whether the life of intact amphibians, the neoteny of the axolotl, or the gigantism of thyroidless tadpoles ends with aging for the simple reason that axolotls can live 50, and normal frogs 12, 15 or 20 years. This complication is a recurring one in studies of aging. The vast literature on endocrinology and morphogenesis of lower vertebrates cannot be used when discussing this problem due to the lack of statistical data.
Both homeothermic and poikilothermic animals, regardless of whether they have metamorphosis or not, have an earlier phase of active growth and a later phase of active reproduction, each of these phases is characterized by a special type of hormonal regulation, and the second phase is characterized by a relative weakening of the ability to regeneration by enhancing the ability to reproduce. These phases differ in the action of the mechanism that regulates the rate of processes, which functions in the juvenile phase. In mammals, these phases appear to be controlled sequentially by pituitary mechanisms regulating the growth and maturation of the gonads. In lower vertebrates, the process of differentiation and the transition to the functions of an adult organism depends on the pituitary-thyroid balance. Pituitary growth hormone, isolated from mammals, is capable of stimulating growth.
Of particular interest to gerontology is the connection between morphogenesis under the influence of sex hormones and the loss of the ability to regenerate. Grobstein found that in fish from the family Poecilidae, during the period of gonopodium differentiation, under the influence of androgens, the ability to regenerate decreases. He draws an analogy between this process and the loss of the ability to regenerate in the developing limb of tailless amphibians. Such changes are not necessarily associated with an irreversible loss of cell growth ability (such a dependence does not appear, for example, in the case of amphibian limbs); however, the physiological capacity for regeneration can be as complete when we're talking about about an intact animal, as well as the loss of molting ability in the Rhodnius bug when the evocator is lost. Perhaps, as Minot believed, there is a mechanism at work here that induces senile changes.
Fig. 68. Growth constant in humans (boys) according to Quetelet. K 1 and K 4 - growth constants for each period
There is some evidence regarding the influence of hormones on protein anabolism and growth regulation in mammals, and especially in humans. Analysis of these influences does not support the assumption that there is a simple connection between aging and growth arrest. Even less likely is the concept of a single, “leading” hormonal inhibitor that can be removed from the general program of progressive changes during development. This program, embedded in a person, is characterized by all the complexities of a dynamic system in which homeostasis coexists with changes. Much of the available information is preliminary, and no studies have yet been conducted that include the aging period. It is clear, however, that in humans, and probably in some but not all mammals, the “anabolic” stimulus that determines protein synthesis does not remain the same throughout life. In an adult organism, it is closely related to the sexual cycle. What is the difference in hormonal regulation of growth between organisms with limited (for example, humans) and unlimited (for example, rats) growth has not yet been clarified; Very little is also known about the hormonal regulation of growth in lower vertebrates. However, the available data are quite sufficient to consider any static idea of growth cessation under the influence of a deficiency of any one hormone unacceptable. It is perhaps more correct to consider the period before and after puberty as separate stages, separated by something equivalent to biochemical metamorphosis.
Human growth, like that of Daphnia (p. 151), is characterized by two overlapping cycles, one pre-puberty and the other post-puberty (Figs. 67, 68). The most active phase of the first cycle occurs in the first 6 months of life. This cycle, according to Kinsella, is almost entirely regulated by pituitary growth hormone. The second cycle appears to be regulated directly by anabolic steroid hormones secreted by the gonads and adrenal cortex. During both cycles, some minimal secretion of thyroid hormone is required to support growth and development.
During puberty, in response to the action of the pituitary gonadotropin hormone, the gonads secrete steroid hormones that directly stimulate the growth of bones and soft tissues. The process of bone growth in humans, however, is limited, since the same hormones determine the maturation of the skeletal system and the ossification of epiphyseal cartilage. There is reason to believe that these hormones also suppress the formation of pituitary growth hormone - probably through a negative feedback system in which the control signal is the intensity of protein synthesis. It is extremely interesting that men after castration sometimes experience symptoms of acromegaly or obvious gigantism, however, along with polyuria and diabetes insipidus. In girls, after reaching puberty, growth appears to be mainly due to the activity of the adrenal glands, since the growth-stimulating effect of estrogens and progesterone is less pronounced (except for their role in the retention of Ca and PO 4), compared with the corresponding effect of androgens. It is generally accepted that thyroxine enhances the action of pituitary growth hormone in mammals during the period of puberty, and also accelerates differentiation. This, in all likelihood, does not apply to tailless amphibians, in which thiouracil causes false gigantism and which, apparently, are characterized by thyro-pituitary equilibrium: one hormone causes differentiation, and the other causes growth and stay in a “juvenile” state.
This picture, which requires detail, agrees quite well with the known data on the role of insufficiency of various hormones in the pathogenesis of dwarfism and gigantism in humans. The onset of puberty coincides with the completion of maturation of the skeletal system. Administration of growth hormone makes it possible to delay the ossification of epiphyseal cartilage and the transition to the subsequent period of growth; a similar phenomenon occurs with spontaneous gigantism. At the same time, complete elimination of the influence of the gonads by castration before reaching puberty does not have a pronounced effect on life expectancy; It was noted that in cases of constitutional precocious maturation, when it is completed completely by the age of 6, the duration of the upcoming life, apparently, does not differ from normal.
Some researchers believed that aging of mammals comes down to a decrease in the formation of growth hormone and is caused by the action of the pituitary gonadotropic hormone on somatic tissues. If we proceed from the fact that aging is essentially the result of differentiation, then everything said is undoubtedly true. However, from an experimental perspective, the question is rather: to what extent can the administration of one or more “anabolic” hormones alter the ability of an adult animal to maintain homeostasis? It is possible that growth hormone itself is the “juvenile hormone” of the mammal during the period before reaching adulthood. Its main role is to stimulate protein synthesis and body growth. (Note that insect juvenile hormone is also found in the organs of mammals; what its function there, if any, is completely unknown.) Changes in the rate of protein synthesis and nitrogen retention capacity, as well as slower growth, are two of the most closely related to aging. The introduction of growth hormone “surprisingly creates the ratios in the content of nitrogen, fat and water in the body, characteristic of adolescence, even in old animals,” but does not increase their life expectancy. Undoubtedly, the specificity of the tissue response to growth hormone changes; in some mammals, this change coincides with the achievement of maturity and the introduction of a new mechanism that maintains anabolism at a constant level. Experimental studies by Jung in England and Lee in America suggest that up to a certain critical point, the administration of growth hormone only stimulates protein synthesis, and after this point it causes diabetes. This is true for humans, cats and dogs, but not for rats and, apparently, not for mice, which are characterized by continuous growth. The incidence of diabetes in combination with spontaneous acromegaly shows that changes in the specificity of the tissue response are associated with the influence of both endogenous and exogenous hormones. Data on the existence of a special diabetogenic principle are not very convincing. Todorov, using chemical methods, discovered age-related changes in the tissue response to growth hormone even in rats; The latent period for the response of DNA and RNA from rat liver to this hormone definitely increases with age. Complete removal of the anterior pituitary gland in adult rats causes cessation of growth; however, no other data that would be relevant to the problem of aging can be obtained.
IN experimental studies Highly purified growth hormone, when administered repeatedly to rats, reduced nitrogen retention and growth rate. These experiments, however, were invariably conducted with heterologous hormones (usually from cattle); therefore, as in the case of antigonadotropic effects, the increase in tissue reactivity cannot be given physiological significance.
Of the other hormones that influence the processes of growth and differentiation, thyroid-stimulating hormone of the pituitary gland in most studied mammals (rats, rabbits, mice, large cattle) exhibits maximum activity, apparently, at the onset of puberty; then there is a decrease in activity, which, however, has never been traced to old age. The decrease in the intensity of general metabolism with age, which has often been associated with a decrease in the ability to grow, taken as an indicator of “physiological aging,” apparently is expressed in a weakening of the activity of the thyroid gland and, possibly, cellular reactivity, since after thyroidectomy in rats there was no there is a decrease in heart rate and O 2 consumption, and in old normal rats there is a weaker response to the administration of thyroxine. The decrease in heat production in older people is perhaps as much due to involution of the thyroid gland as to muscle atrophy; the ability of the thyroid gland to respond to thyrotropin appears to remain unimpaired.
The phenomena observed by McKay during dietary restriction can be considered as the consequences of “alimentary” hypophysectomy. This affects the formation of both growth hormone and gonadotropic hormone. As a result, there is a decrease in the overall effectiveness of a single integrating system of growth and development. The separation of these systems in mammals is a very interesting, but practically difficult to solve problem. Developmental delay by restricting the diet significantly delays the onset of estrus, but still cannot completely prevent it. McKay, Sperling and Barnes found that rats that were arrested in their development eventually lost the ability to resume growth if the delay was prolonged.
The school of Lee and Evans began to develop the problem of selective interference with differentiation in mammals. Hypophysectomy of 6-day-old rat pups does not affect teething and vision, but suppresses all phases of sexual development. Hypophysectomized animals eventually die from paralysis caused by compression of the brain because their brains grow faster than their brains. Rats that survived the operation remained in good condition. In these rats, growth rate was only marginally lower than in control rats that were not hypophysectomized. Their skeletal development proceeded normally, but organ differentiation and puberty characteristic of adults were absent. Observations of three such "metetelic" rats were carried out for 200-300 days in the hope that they would develop gigantism. It would be extremely interesting to know what their life expectancy would have been and what senile changes they would eventually develop.
It has not yet been possible to selectively suppress the formation of gonadotropin hormone, although studies with sparrow extracts (Lithospermum) allow hope for “dismemberment” of the pituitary effect with the help of chemical antagonists. The effect of artificially induced precocity on lifespan in mammals (except in humans, in whom precociousness sometimes occurs spontaneously) does not appear to have been studied. Mice, which mature very early, are not ideal subjects for such research, and experiments with longer-lived mammals present well-known practical difficulties.
Growth is one of the indicators characterizing the child’s health and the normal regulation of the body’s activities. In April 2006 World Organization New health standards for children's growth have been published. They say that every child, under optimal conditions, has equal potential to regulate height and weight. Naturally, every child is different, and every child has their own developmental characteristics, but global average growth rates are strikingly similar. If the skeletal system develops more slowly than the child develops, the child will be shorter than his peers. Such features of the development of the skeletal system are called the biological age of the child.
The developed standards contribute to the early detection of malnutrition, overweight, obesity and other conditions related to the regulation of child growth; they are important for taking appropriate measures. They also indicate that different heights, to a greater extent than genetic and ethnic factors, are based on nutritional characteristics, environment and health care.
Thus, for normal growth regulation it is necessary good nutrition, favorable psycho-emotional environment, normal hormonal balance and absence of chronic diseases. There are two more things that can influence growth. These include family predisposition and characteristics of the course of pregnancy, the so-called genetic and intrauterine factors.
However, the regulation of growth is largely determined by the genetic “program” inherent in a person. We often meet people whose height is significantly higher than average. This indicates that if this is done for a longer period of time in a person, his height can be increased above the average norm established by nature. This has been very clearly manifested in the last 50 years, when there was a widespread acceleration in the growth of children, especially pronounced in economic terms. developed countries solving nutrition problems. And in our country such a process has been observed; at present it has stopped, since the majority of children are reaching their genetic growth limit. So, according to A. Baranov, academician of the Russian Academy of Medical Sciences, director of the Research Institute of Children's Health, the average height of Russians is decreasing: . The average height of a Russian resident is 170 cm. However, the decline is likely to continue. For example, now in the Urals the average height of a newborn is 50 centimeters (in 1980, throughout the USSR, the average height of a newborn was 51.7 cm). Apparently, these Russians will become even shorter when they grow up.
On the other hand, being very tall can also be a sign of being unhealthy. Some diseases can actually manifest themselves in this way. First of all, these are pituitary tumors, so-called somatotropinomas. The external manifestations of this disease in children and adults are different. In children (when the growth plates are open), the release of growth hormone leads to an increase in height. In adults (when the growth zones are already closed), the clinical picture of the disease is manifested by an increase in individual parts of the body (the nose and other parts of the body become larger), and there is a violation of body proportions. In any case, an examination is necessary, first of all magnetic resonance imaging of the brain, examination by an endocrinologist. Further treatment will depend on the results obtained.