Study of the hormonal background: norm and pathology. Release of hormones that regulate human and animal growth Bone growth is regulated by a hormone

The date: 26.06.2020

Effector pituitary hormones

These include a growth hormone(GR), prolactin(lactotropic hormone - LTH) of the adenohypophysis and melanocyte-stimulating hormone(MSH) of the intermediate lobe of the pituitary gland (see Fig. 1).

Rice. 1. Hypothalamic and pituitary hormones (RG-releasing hormones (liberins), ST - statins). Explanations in the text

Somatotropin

Growth hormone (somatotropin, somatotropic hormone STH)- a polypeptide consisting of 191 amino acids, is formed by red acidophilic cells of the adenohypophysis - somatotrophs. The half-life is 20-25 minutes. It is transported in the blood in a free form.

GR targets are cells of bone, cartilage, muscle, adipose tissue and liver. It has a direct effect on target cells through stimulation of 1-TMS receptors with catalytic tyrosine kinase activity, as well as an indirect effect through somatomedins - insulin-like growth factors (IGF-I, IGF-II) formed in the liver and other tissues in response to the action GR.

Characteristics of somatomedins

The content of GH in depends on age and has a pronounced daily periodicity. The highest content of the hormone was noted in early childhood with a gradual decrease: from 5 to 20 years - 6 ng / ml (with a peak during puberty), from 20 to 40 years - about 3 ng / ml, after 40 years - 1 ng / ml ml. During the day, GH enters the blood cyclically - the absence of secretion alternates with “explosions of secretion” with a maximum during sleep.

Main functions of GH in the body

Growth hormone has a direct effect on the metabolism in target cells and the growth of organs and tissues, which can be achieved both by its direct action on target cells and by the indirect action of somatomedins C and A (insulin-like growth factors) released by hepatocytes and chondrocytes when exposed to on them GR.

Growth hormone, like insulin, facilitates the uptake and utilization of glucose by cells, stimulates glycogen synthesis, and is involved in maintaining normal blood glucose levels. At the same time, GH stimulates gluconeogenesis and glycogenolysis in the liver; the insulin-like effect is replaced by a contra-insular one. As a result, hyperglycemia develops. GH stimulates the release of glucagon, which also contributes to the development of hyperglycemia. At the same time, the formation of insulin increases, but the sensitivity of cells to it decreases.

Growth hormone activates lipolysis in adipose tissue cells, promotes the mobilization of free fatty acids into the blood and their use by cells for energy.

Growth hormone stimulates protein anabolism, facilitating the entry of amino acids into the cells of the liver, muscles, cartilage and bone tissue and activating protein and nucleic acid synthesis. This helps to increase the intensity of basal metabolism, increase the mass of muscle tissue, and accelerate the growth of tubular bones.

The anabolic effect of GH is accompanied by an increase in body weight without the accumulation of fat. At the same time, GH contributes to the retention of nitrogen, phosphorus, calcium, sodium and water in the body. As already mentioned, GH has an anabolic effect and stimulates growth through increased synthesis and secretion in the liver and cartilage of growth factors that stimulate chondrocyte differentiation and bone lengthening. Under the influence of growth factors, the supply of amino acids to myocytes and the synthesis of muscle proteins increase, which is accompanied by an increase in the mass of muscle tissue.

The synthesis and secretion of GH are regulated by the hypothalamic hormone somatoliberin (GHR - growth hormone releasing hormone), which enhances the secretion of GH and somatostatin (SS), which inhibits the synthesis and secretion of GH. The level of GH progressively increases during sleep (the maximum content of the hormone in the blood falls on the first 2 hours of sleep and at 4-6 am). Hypoglycemia and lack of free fatty acids (during fasting), an excess of amino acids (after eating) in the blood increase the secretion of somatoliberin and GH. The hormones cortisol, the level of which increases with pain stress, trauma, exposure to cold, emotional arousal, T 4 and T 3, enhance the effect of somatoliberin on somatotrophs and increase GR secretion. Somatomedins, high levels of glucose and free fatty acids in the blood, exogenous GH inhibit the secretion of pituitary GH.

Rice. Regulation of somatotropin secretion

Rice. The role of somatomedins in the action of somatotropin

The physiological consequences of excessive or insufficient secretion of GH were studied in patients with neuroendocrine diseases, in which the pathological process was accompanied by impaired endocrine function of the hypothalamus and (or) pituitary gland. A decrease in the effects of GH has also been studied in violation of the response of target cells to the action of GH, associated with defects in the hormone-receptor interaction.

Rice. The circadian rhythm of somatotropin secretion

Excessive secretion of GH in childhood is manifested by a sharp acceleration of growth (more than 12 cm / year) and the development of gigantism in an adult (body height in men exceeds 2 m, and in women - 1.9 m). Body proportions are preserved. Hyperproduction of the hormone in adults (for example, with a pituitary tumor) is accompanied by acromegaly - a disproportionate increase in individual parts of the body that still retain the ability to grow. This leads to a change in a person's appearance due to disproportionate development of the jaws, excessive elongation of the limbs, and may also be accompanied by the development of diabetes mellitus due to the development of insulin resistance due to a decrease in the number of insulin receptors in cells and activation of the synthesis of the insulinase enzyme in the liver, which destroys insulin.

The main effects of somatotropin

Metabolic:

protein metabolism: stimulates protein synthesis, facilitates the entry of amino acids into cells;
fat metabolism: stimulates lipolysis, the level of fatty acids in the blood rises and they become the main source of energy;
carbohydrate metabolism: stimulates the production of insulin and glucagon, activates liver insulinase. In high concentrations, it stimulates glycogenolysis, the blood glucose level rises, and its utilization is inhibited.

Functional:

causes a delay in the body of nitrogen, phosphorus, potassium, sodium, water;
enhances the lipolytic effect of catecholamines and glucocorticoids;
activates growth factors of tissue origin;
stimulates milk production;
is species specific.

Table. Manifestations of changes in somatotropin production

Insufficient secretion of GH in childhood or a violation of the connection of the hormone with the receptor is manifested by inhibition of the growth rate (less than 4 cm / year) while maintaining the proportions of the body and mental development. At the same time, an adult develops dwarfism (the height of women does not exceed 120 cm, and men - 130 cm). Dwarfism is often accompanied by sexual underdevelopment. The second name of this disease is pituitary dwarfism. In an adult, a lack of GH secretion is manifested by a decrease in basal metabolism, skeletal muscle mass, and an increase in fat mass.

Prolactin

Prolactin (lactotropic hormone)- LTG) is a polypeptide consisting of 198 amino acids, belongs to the same family as somatotronin and has a similar chemical structure with it.

It is secreted into the blood by yellow lactotrophs of the adenohypophysis (10-25% of its cells, and during pregnancy - up to 70%), transported by the blood in a free form, the half-life is 10-25 minutes. Prolactin has an effect on target cells of the mammary glands through stimulation of 1-TMS receptors. Prolactin receptors are also found in the cells of the ovaries, testicles, uterus, as well as the heart, lungs, thymus, liver, spleen, pancreas, kidneys, adrenal glands, skeletal muscles, skin and some parts of the central nervous system.

The main effects of prolactin are associated with the implementation of the reproductive function. The most important of them is to ensure lactation by stimulating the development of glandular tissue in the mammary gland during pregnancy, and after childbirth - the formation of colostrum and its transformation into mother's milk (the formation of lactalbumin, milk fats and carbohydrates). At the same time, it does not affect the very secretion of milk, which occurs reflexively during the feeding of the baby.

Prolactin inhibits the release of gonadotropins by the pituitary gland, stimulates the development of the corpus luteum, reduces the formation of progesterone, and inhibits ovulation and pregnancy during breastfeeding. Prolactin also contributes to the formation of parental instinct in the mother during pregnancy.

Together with thyroid hormones, growth hormone and steroid hormones, prolactin stimulates the production of surfactant by the lungs of the fetus and causes a slight decrease in pain sensitivity in the mother. In children, prolactin stimulates the development of the thymus and is involved in the formation of immune responses.

The production and secretion of prolactin by the pituitary gland is regulated by hormones from the hypothalamus. Prolactostatin is dopamine, which inhibits the secretion of prolactin. Prolactoliberin, the nature of which has not been finally identified, increases the secretion of the hormone. The secretion of prolactin is stimulated by a decrease in the level of dopamine, an increase in the level of estrogen during pregnancy, an increase in the content of serotonin and melatonin, and also in a reflex way when the mechanoreceptors of the nipple of the mammary gland are stimulated during the act of sucking, the signals from which enter the hypothalamus and stimulate the release of prolactoliberin.

Rice. Regulation of prolactin secretion

The production of prolactin increases significantly with anxiety, stress, depression, and severe pain. Inhibit the secretion of prolactin FSH, LH, progesterone.

The main effects of prolactin:

Enhances the growth of the mammary glands
Initiates milk synthesis during pregnancy and lactation
Activates the secretory activity of the corpus luteum
Stimulates the secretion of vasopressin and aldosterone
Participates in the regulation of water-salt metabolism
Stimulates the growth of internal organs
Participates in the realization of the instinct of motherhood
Increases fat and protein synthesis
Causes hyperglycemia
It has an autocrine and paracrine modulating effect in the immune response (prolactin receptors on T-lymphocytes)

Excess hormone (hyperprolactinemia) can be physiological and pathological. An increase in prolactin levels in a healthy person can be observed during pregnancy, breastfeeding, after intense physical exertion, during deep sleep. Pathological hyperproduction of prolactin is associated with pituitary adenoma and can be observed in diseases of the thyroid gland, cirrhosis of the liver and other pathologies.

Hyperprolactinemia can cause menstrual irregularities in women, hypogonadism and decreased function of the sex glands, an increase in the size of the mammary glands, galactorrhea in lactating women (increased production and secretion of milk); in men - impotence and infertility.

A decrease in the level of prolactin (hypoprolactinemia) can be observed with insufficient function of the pituitary gland, prolonged pregnancy, after taking a number of drugs. One of the manifestations is lactation deficiency or its absence.

Melantropin

Melanocyte-stimulating hormone(MSG, melanotropin, intermedin) is a peptide consisting of 13 amino acid residues, formed in the intermediate zone of the pituitary gland in the fetus and newborns. In an adult, this zone is reduced and MSH is produced in limited quantities.

The precursor of MSH is the polypeptide proopiomelanocortin, from which adrenocorticotropic hormone (ACTH) and β-lipotroin are also formed. There are three types of MSH - a-MSH, β-MSH, y-MSH, of which a-MSH is the most active.

The main functions of MSH in the body

The hormone induces the synthesis of the enzyme tyrosinase and the formation of melanin (melanogenesis) through the stimulation of specific 7-TMS receptors associated with G-protein in target cells, which are melanocytes of the skin, hair and retinal pigment epithelium. MSH causes dispersion of melanosomes in skin cells, which is accompanied by darkening of the skin. Such darkening occurs with an increase in the content of MSH, for example, during pregnancy or with adrenal disease (Addison's disease), when not only the level of MSH, but also ACTH and β-lipotropin increases in the blood. The latter, being derivatives of pro-opiomelanocortin, can also enhance pigmentation, and with an insufficient level of MSH in the body of an adult, they can partially compensate for its functions.

Melanthropy:

Activate the synthesis of the enzyme tyrosinase in melanosomes, which is accompanied by the formation of melanin
They are involved in the dispersion of melanosomes in skin cells. Dispersed melanin granules with the participation of external factors (illumination, etc.) are aggregated, giving the skin a dark color
Involved in the regulation of the immune response

Tropic hormones of the pituitary gland

They are formed in the adenogynophysis and regulate the functions of target cells of the peripheral endocrine glands, as well as non-endocrine cells. The glands whose functions are controlled by the hormones of the hypothalamus-pituitary-endocrine gland systems are the thyroid gland, the adrenal cortex, and the gonads.

Thyrotropin

Thyroid-stimulating hormone(TTG, thyrotropin) synthesized by basophilic thyrotrophs of the adenohypophysis, is a glycoprotein consisting of a- and β-subunits, the synthesis of which is determined by various genes.

The structure of the a-subunit of TSH is similar to the subunits in the composition of lugenizing, follicle-stimulating hormones and chorionic gonadotropin formed in the placenta. The a-subunit of TSH is non-specific and does not directly determine its biological action.

a-Subunit of thyrotropin can be contained in the blood serum in an amount of about 0.5-2.0 μg / l. A higher level of its concentration may be one of the signs of the development of a TSH-secreting pituitary tumor and be observed in women after menopause.

This subunit is necessary to impart specificity to the spatial structure of the TSH molecule, in which thyrotropin acquires the ability to stimulate the membrane receptors of thyrocytes of the thyroid gland and cause its biological effects. This TSH structure occurs after non-covalent binding of the a- and β-chains of the molecule. At the same time, the structure of the p-subunit, consisting of 112 amino acids, is the determining determinant for the manifestation of the biological activity of TSH. In addition, to enhance the biological activity of TSH and the rate of its metabolism, glycosylation of the TSH molecule in the rough endoplasmic reticulum and Golgi apparatus of thyrotrophs is necessary.

There are known cases of the presence in children of point mutations of the gene encoding the synthesis (β-chain of TSH), as a result of which the P-subunit of an altered structure is synthesized, unable to interact with the a-subunit and form a biologically active tnrotropin. Clinical signs of hypothyroidism are observed in children with a similar pathology.

The concentration of TSH in the blood ranges from 0.5 to 5.0 mcU / ml and reaches its maximum between midnight and four o'clock. Secretion of TSH is minimal in the afternoon. This fluctuation in the content of TSH at different times of the day does not significantly affect the concentrations of T 4 and T 3 in the blood, since the body has a large pool of extrathyroid T 4 . The half-life of TSH in plasma is about half an hour, and its production per day is 40-150 mU.

The synthesis and secretion of thyrotropin is regulated by many biologically active substances, among which the hypothalamic TRH and free T4, T3 secreted by the thyroid gland into the blood are the leading ones.

Thyrotropin-releasing hormone is a hypothalamic neuropeptide that is produced in the neurosecretory cells of the hypothalamus and stimulates the secretion of TSH. TRH is secreted by the cells of the hypothalamus into the blood of the portal vessels of the pituitary gland through the axovasal synapses, where it binds to thyrotrophic receptors, stimulating the synthesis of TSH. The synthesis of TRH is stimulated at a reduced level in the blood of T 4 , T 3 . The secretion of TRH is also controlled by the level of thyrotropin through a negative feedback channel.

TRH has a variety of effects in the body. It stimulates the secretion of prolactin, and with elevated levels of TRH in women, the effects of hyperprolactinemia can be observed. This condition can develop with reduced thyroid function, accompanied by an increase in TRH levels. TRH is also found in other structures of the brain, in the walls of the organs of the gastrointestinal tract. It is assumed that it is used in synapses as a neuromodulator and has an antidepressant effect in depression.

Table. The main effects of thyrotropin

The secretion of TSH and its level in plasma are inversely proportional to the concentration of free T 4 , T 3 and T 2 in the blood. These hormones suppress the synthesis of thyrotropin through the negative feedback channel, acting both directly on the thyrotrophs themselves and through a decrease in the secretion of TRH by the hypothalamus (neurosecretory cells of the hypothalamus that form TRH and pituitary thyrotrophs are target cells of T 4 and T 3). With a decrease in the concentration of thyroid hormones in the blood, for example, with hypothyroidism, there is an increase in the percentage of the population of thyrotrophs among the cells of the adenohypophysis, an increase in the synthesis of TSH and an increase in its level in the blood.

These effects are a consequence of the stimulation of TR 1 and TR 2 receptors by thyroid hormones, which are expressed in pituitary thyrotrophs. Experiments have shown that the TR 2 isoform of the TG receptor has a leading role in the expression of the TSH gene. Obviously, a violation of the expression, a change in the structure or affinity of thyroid hormone receptors can be manifested by a violation of the formation of TSH in the pituitary gland and the function of the thyroid gland.

Somatostatin, serotonin, dopamine, as well as IL-1 and IL-6, the level of which increases during inflammatory processes in the body, have an inhibitory effect on the secretion of TSH by the pituitary gland. Inhibition of TSH secretion by norepinephrine and glucocorticoid hormones, which can be observed under conditions of stress. The level of TSH increases in hypothyroidism, may increase after partial thyroidectomy and (or) after radioiodine therapy of thyroid neoplasms. This information should be taken into account by doctors when examining patients with diseases of the thyroid system for the correct diagnosis of the causes of the disease.

Thyrotropin is the main regulator of thyrocyte functions, accelerating almost every step in the synthesis, storage and secretion of triglycerides. Under the action of TSH, the proliferation of thyrocytes is accelerated, the size of the follicles and the thyroid gland itself increases, and its vascularization increases.

All these effects are the result of a complex set of biochemical and physicochemical reactions that occur after the binding of thyrotropin to its receptor located on the basement membrane of the thyrocyte, and the activation of adenylate cyclase associated with the G protein, which leads to an increase in the level of cAMP, activation of cAMP dependent protein kinases A, which phosphorylate key thyrocyte enzymes. In thyrocytes, the level of calcium rises, the absorption of iodide increases, its transport and inclusion with the participation of the enzyme thyroperoxidase into the structure of thyroglobulin is accelerated.

Under the influence of TSH, the processes of formation of pseudopodia are activated, accelerating the resorption of thyroglobulin from colloid into thyrocytes, the formation of colloid drops in the follicles and the hydrolysis of thyroglobulin in them under the action of lysosomal enzymes are accelerated, the metabolism of thyrocyte is activated, which is accompanied by an increase in the rate of absorption of glucose and oxygen by thyrocytes, glucose oxidation, accelerates synthesis of proteins and phospholipids, which are necessary for the growth and increase in the number of thyrocytes and the formation of follicles. In high concentrations and with prolonged exposure, thyrotropin causes proliferation of thyroid cells, an increase in its mass, size (goiter), an increase in hormone synthesis and the development of its hyperfunction (with a sufficient amount of iodine). In the body, the effects of an excess of thyroid hormones develop (increased excitability of the central nervous system, tachycardia, increased basal metabolism and body temperature, bulging eyes, and other changes).

Lack of TSH leads to rapid or gradual development of hypothyroidism (hypothyroidism). A person develops a decrease in basal metabolism, drowsiness, lethargy, adynamia, bradycardia and other changes.

Thyrotropin, stimulating receptors in other tissues, increases the activity of selenium-dependent deiodinase, which converts thyroxine into a more active triiodothyronine, as well as the sensitivity of their receptors, thereby “preparing” tissues for the effects of thyroid hormones.

Violation of the interaction of TSH with the receptor, for example, when the structure of the receptor or its affinity for TSH is changed, may underlie the pathogenesis of a number of thyroid diseases. In particular, a change in the structure of the TSH receptor as a result of a mutation of the gene encoding its synthesis leads to a decrease or lack of sensitivity of thyrocytes to the action of TSH and the development of congenital primary hypothyroidism.

Since the structure of the a-subunits of TSH and gonadotropin is the same, at high concentrations gonadotropin (for example, with chorionepitheliomas) can compete for binding to TSH receptors and stimulate the formation and secretion of TG by the thyroid gland.

The TSH receptor is able to bind not only to thyrotropic, but also to autoantibodies - immunoglobulins that stimulate or block this receptor. Such binding occurs in autoimmune thyroid diseases and in particular in autoimmune thyroiditis (Graves' disease). The source of these antibodies is usually B-lymphocytes. Thyroid-stimulating immunoglobulins bind to the TSH receptor and act on the thyrocytes of the gland in a similar way to how TSH works.

In other cases, autoantibodies may appear in the body that block the interaction of the receptor with TSH, as a result of which atrophic thyroiditis, hypothyroidism, and myxedema may develop.

Mutations in the genes encoding the synthesis of the TSH receptor can lead to the development of their resistance to TSH. With complete resistance to TSH, the thyroid gland is gynoplastic, unable to synthesize and secrete sufficient amounts of thyroid hormones.

Depending on the link of the hypothalamic-hyophyseal-thyroid system, the change in which led to the development of disorders in the functioning of the thyroid gland, it is customary to distinguish: primary hypo- or hyperthyroidism, when the disorder is directly related to the thyroid gland; secondary, when the disorder is caused by changes in the pituitary gland; tertiary - in the hypothalamus.

Lutropin

Gonadotropins - follicle stimulating hormone(FSH), or follitropin and luteinizing hormone(LG), or lutropin, - are glycoproteins, are formed in different or the same basophilic cells (gonadotrophs) of the adenohypophysis, regulate the development of endocrine functions of the gonads in men and women, acting on target cells through stimulation of 7-TMS receptors and increasing their cAMP levels. During pregnancy, FSH and LH can be produced in the placenta.

The main functions of gonadotropins in the female body

Under the influence of an increasing level of FSH during the first days of the menstrual cycle, the primary follicle matures and the concentration of estradiol in the blood increases. The action of the peak LH level in the middle of the cycle is the direct cause of the rupture of the follicle and its transformation into a corpus luteum. The latent period from the time of the peak concentration of LH to ovulation is from 24 to 36 hours. LH is a key hormone that stimulates the production of progesterone and estrogen in the ovaries.

The main functions of gonadotropins in the male body

FSH promotes testicular growth, stimulates Csrtoli cells and promotes their production of androgen-binding protein, and also stimulates the production of inhibin polypeptide by these cells, which reduces the secretion of FSH and GH. LH stimulates the maturation and differentiation of Leydig cells, as well as the synthesis and secretion of testosterone by these cells. The combined action of FSH, LH and testosterone is necessary for the implementation of spermatogenesis.

Table. Main effects of gonadotropins

The secretion of FSH and LH is regulated by the hypothalamic gonadotropin-releasing hormone (GH), also called gonadoliberin and luliberin, which stimulates their release into the blood, primarily FSH. An increase in the content of estrogens in the blood of women on certain days of the menstrual cycle stimulates the formation of LH in the hypothalamus (positive feedback). The action of estrogens, progestins and the hormone inhibin inhibit the release of GHRH, FSH and LH. Inhibits the formation of FSH and LH prolactin.

The secretion of gonadotropins in men is regulated by GH (activation), free testosterone (inhibition) and inhibin (inhibition). In men, the secretion of GH is continuous, in contrast to women, in whom it occurs cyclically.

In children, the secretion of gonadotropins is inhibited by the hormone of the pineal gland - melatonin. At the same time, low levels of FSH and LH in children are accompanied by late or insufficient development of primary and secondary sexual characteristics, late closure of growth zones in the bones (lack of estrogen or testosterone), and pathologically high growth or gigantism. In women, the lack of FSH and LH is accompanied by a violation or cessation of the menstrual cycle. In breastfeeding mothers, these cycle changes can be quite pronounced due to high levels of prolactin.

Excess secretion of FSH and LH in children is accompanied by early puberty, closure of growth zones, and hypergonadal short stature.

Corticotropin

adrenocorticotropic hormone(ACTH, or corticotropin) is a peptide consisting of 39 amino acid residues, synthesized by corticotrophs of the adenohypophysis, acts on target cells, stimulating 7-TMS receptors and increasing the level of cAMP, the half-life of the hormone is up to 10 minutes.

Main effects of ACTH subdivided into adrenal and extra-adrenal. ACTH stimulates the growth and development of the fascicular and reticular zones of the adrenal cortex, as well as the synthesis and release of glucocorticoids (cortisol and corticosterone by the cells of the fascicular zone and, to a lesser extent, sex hormones (mainly androgens) by the cells of the reticular zone. ACTH weakly stimulates the release of the mineralocorticoid aldosterone by the cells of the glomerular zone adrenal cortex.

Table. Main effects of corticotropin

The extra-adrenal action of ACTH is the action of the hormone on the cells of other organs. ACTH has a lipolytic effect in adipocytes and promotes an increase in the level of free fatty acids in the blood; stimulates the secretion of insulin by pancreatic β-cells and contributes to the development of hypoglycemia; stimulates the secretion of growth hormone by somatotrophs of the adenohypophysis; enhances skin pigmentation, similar to MSH, with which it has a similar structure.

Regulation of ACTH secretion is carried out by three main mechanisms. Basal secretion of ACTH is regulated by the endogenous rhythm of corticoliberin secretion by the hypothalamus (maximum level in the morning at 6-8 hours, minimum - at 22-2 hours). Increased secretion is achieved by the action of a larger amount of corticoliberin, which is formed during stressful effects on the body (emotions, cold, pain, physical activity, etc.). The level of ACTH is also controlled by a negative feedback mechanism: it decreases with an increase in the content of the glucocorticoid hormone cortisol in the blood and increases with a decrease in the level of cortisol in the blood. An increase in cortisol levels is also accompanied by inhibition of the secretion of corticoliberin by the hypothalamus, which also leads to a decrease in the production of ACTH by the pituitary gland.

Rice. Regulation of corticotropin secretion

Excessive secretion of ACTH occurs during pregnancy, as well as during primary or secondary (after removal of the adrenal glands) hyperfunction of corticotrophs of the adenohypophysis. Its manifestations are diverse and are associated both with the effects of ACTH itself and with its stimulating effect on the secretion of hormones by the adrenal cortex and other hormones. ACTH stimulates the secretion of growth hormone, the level of which is important for normal growth and development of the body. An increase in ACTH levels, especially in childhood, may be accompanied by symptoms due to excessive production of growth hormone (see above). With an excessive level of ACTH in children due to stimulation of the secretion of sex hormones by the adrenal glands, early puberty, an imbalance of male and female sex hormones, and the development of signs of masculinization in women can be observed.

At high concentrations in the blood, ACTH stimulates lipolysis, protein catabolism, and the development of excessive skin pigmentation.

Deficiency of ACTH in the body leads to insufficient secretion of pyococorticoids by the cells of the adrenal cortex, which is accompanied by metabolic disorders and a decrease in the body's resistance to the adverse effects of environmental factors.

ACTH is formed from a precursor (pro-opiomelanocortin), from which a- and β-MSH are also synthesized, as well as β- and y-lipotropins and endogenous morphine-like peptides - endorphins and enkephalins. Lipotropins activate lipolysis, and endorphins and enkephalins are important components of the antinociceptive (pain) system of the brain.

Although most of the endocrine glands begin to function even 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 for it. Any violations and deviations in the work of the regulatory neuroendocrine systems that occurred during the birth of a child can have a serious impact on the state of his health throughout his subsequent life.

The first - urgent - reaction of the neuroendocrine system of the fetus 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 of live birth, but in itself it is the result of the most complex nervous, hormonal and metabolic effects. In the 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 increases rapidly, 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 experiencing natural birth stress have significantly lower levels of catecholamines and thyroid hormones in the blood, which negatively affects their lung function during the first day of life. As a result, their brain suffers from some lack of oxygen, and this may to some extent affect later.

Hormonal regulation of growth

The hypothalamus secretes two opposing hormones - releasing factor and somatostatin, which are sent to the adenohypophysis 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 - an increase in the concentration of the 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 starvation, 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. Indeed, 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 secreted by the pituitary gland has two different effects on the cells of the body. The first - direct - action is that the cells increase the breakdown of previously accumulated reserves of carbohydrates and fats, their mobilization for the needs of energy and plastic metabolism. The second - mediated - 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 same processes that are 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, then the child does not grow up 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 growth of a 7-10-year-old child in adulthood). 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 is already completed under the influence of sex hormones, a acromegaly- limbs, hands and feet, nose, chin and other end parts of the body, as well as the tongue and digestive organs are disproportionately lengthened. Violation 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 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 blood of the fetus 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 approximately at a constant level, which is 2-3 times higher than the level of adults. It is significant that in the same period the most rapid growth processes are completed before the onset of puberty. Then comes a period of significant decrease in the level of the hormone - and growth is inhibited. A new increase in the level of growth hormone in boys is noted after 13 years, and its maximum is noted at 15 years, i.e. just at the time of the most intense increase in body size in adolescents. By the age of 20, the content of growth hormone in the blood is set at a typical adult level.

With the onset of puberty, sex hormones that stimulate protein anabolism are actively involved in the regulation of growth processes. It is under the action 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 precocious puberty, the growth of the body in length may begin too early, but it will end early, and as a result, the boy will remain a “undersize”.

Androgens also stimulate increased growth of the muscles and cartilaginous parts of the larynx, as a result of which the voice “breaks” in boys, it becomes much lower. The anabolic effect of androgens extends to all the 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.

On the throughout For many years, it was believed that the production of growth hormone stops in adulthood, which is not true. As very old people grow older, hormone production slowly declines to 25% of youthful levels.

secretion of growth hormone unstable. The mechanism of control of somatotropin production is not well understood, but some stimulating factors mediating individual fluctuations in its secretion appear to be: (1) starvation, especially of protein, (2) hypoglycemia or low concentration of fatty acids in the blood; (3) physical activity, (4) emotions; (5) trauma. The concentration of growth hormone increases during the first 2 hours of deep sleep.

Normal levels of growth hormone in the plasma of an adult ranges from 1.6 to 3 ng / ml; in children and adolescents, it is about 6 ng / ml. This level can rise up to 50 ng/ml as a result of prolonged fasting.

In emergency situations hypoglycemia is a more powerful stimulator of growth hormone secretion than a sharp decrease in protein intake. On the contrary, under conditions of chronic stress, growth hormone secretion seems to be more related to protein deficiency in the cell than to the degree of glucose deficiency. For example, the extremely high levels of growth hormone observed during fasting are closely correlated with the degree of protein deficiency.

The figure shows the dependence growth hormone levels from protein deficiency and the effect of introducing protein into the diet. The first column shows a very high level of growth hormone in children with severe protein deficiency due to lack of it, forming a condition called kwashiorkor; the second column shows the level of somatotropin in the same children on day 3 after the start of treatment by introducing an excess amount of carbohydrates into the diet; it is obvious that carbohydrates do not reduce the concentration of growth hormone in plasma. The third and fourth columns show the level of somatotropin on days 3 and 25 after the introduction of proteins into the diet, which is accompanied by a decrease in the concentration of the hormone.

Received results prove that with a serious protein deficiency, the normal caloric content of the diet alone is not able to stop the excess production of growth hormone. Correction of protein deficiency is a condition for the normalization of growth hormone production.

Among the previously reviewed factors, which change the production of growth hormone, one caused bewilderment of physiologists trying to unravel the mystery of the regulation of growth hormone secretion. It is known that its production is regulated by two hormones secreted by the hypothalamus and then transported to the anterior pituitary gland through the portal hypothalamic-pituitary system: growth hormone-releasing hormone and growth hormone-inhibiting hormone (the latter is called somatomedin). Both are polypeptides. Growth hormone-releasing hormone consists of 44 amino acid residues, somatostatin - of 14.

Regions hypothalamus, responsible for the production of HRRG, are the ventromedial nuclei. This is the same area of the hypothalamus that is sensitive to blood glucose concentration and causes satiety in hyperglycemia and hunger in hypoglycemic states. Somatostatin secretion is regulated by closely spaced structures in the hypothalamus, so it is reasonable to assume that some of the same signals that guide eating behavior also change growth hormone levels.

Similarly signals, indicating emotions, stress, trauma, can trigger hypothalamic control of somatotropin secretion. It has been experimentally shown that catecholamines, dopamine and serotonin, each of which is released by different neuronal systems of the hypothalamus, increase the rate of growth hormone production.

To a greater extent regulation of growth hormone secretion may be mediated by growth hormone-releasing hormone than by somatostatin. GRH stimulates the secretion of growth hormone by interacting with specific receptors on the outer surface of the membrane of the corresponding cells of the adenohypophysis. Receptors activate the adenylate cyclase system of the cell, increasing the level of cyclic adenosine monophosphate. This is accompanied by both short-term and long-term effects. Short-term effects are to increase the transport of calcium ions into the cell; after a few minutes, this leads to the fusion of growth hormone vesicles with the cell membrane and the release of the hormone into the blood. Long-term effects are mediated by activation of transcriptional processes in the nucleus and increased production of new growth hormone molecules.

If the hormone growth is introduced directly into the blood of experimental animals for several hours, the rate of production of their own hormone decreases. This indicates that growth hormone production is regulated by a negative feedback mechanism, which is true for most hormones. It cannot be definitely said whether the negative feedback mechanism is provided by a decrease in the production of growth hormone-releasing hormone or by the release of somatostatin, which inhibits the production of growth hormone.

Our knowledge on the regulation of growth hormone secretion not enough to paint a complete picture. However, due to the extremely high secretion of somatotropin during fasting and its extremely important long-term effects on protein synthesis and growth processes, it can be assumed that the most important mechanism for regulating prolonged secretion of growth hormone is the concentration of nutrients in tissues as a long-term characteristic of providing nutrition to the tissues themselves, especially the level proteins. In this regard, nutritional deficiency or an increase in the protein demand of tissues, for example, during extreme physical exertion, and as a result, a high need for muscle tissue in nutrients, is one of the ways to stimulate the production of growth hormone. In turn, growth hormone ensures the synthesis of new proteins against the background of protein transformations already taking place in cells.

Educational video pituitary hormones in normal and pathological conditions

In case of problems with viewing, download the video from the page

Somatotropin, or growth hormone, from the group of peptides is produced by the body in the anterior pituitary gland, but the secretion of the substance can be increased naturally. The presence of this component in the body enhances lipolysis, which burns subcutaneous fat, and builds muscle mass. For this reason, it is of particular interest to athletes who seek to improve their athletic performance. To achieve this, it is worth studying in more detail the synthesis process and other features of this substance.

What is somatotropin

This is the name of a peptide hormone synthesized by the anterior pituitary gland. The main property is the stimulation of cell growth and repair, which contributes to the growth of muscle tissue, bone compaction. From the Latin "soma" meaning body. The recombinant hormone got its name due to its ability to accelerate growth in length. Somatotropin belongs to the family of polypeptide hormones along with prolactin and placental lactogen.

Where is formed

This substance is produced in the pituitary gland - a small endocrine gland, about 1 cm. It is located in a special recess at the base of the brain, which is also called the "Turkish saddle". A cellular receptor is a protein with a single intramembrane domain. The pituitary gland is controlled by the hypothalamus. It stimulates or inhibits the process of hormonal synthesis. The production of somatotropin has a wave-like character - several bursts of secretion are observed during the day. The largest number is noted 60 minutes after falling asleep at night.

What is it needed for

Already by the name it can be understood that somatropin is necessary for the growth of bones and the body as a whole. For this reason, it is more actively produced in children and adolescents. At the age of 15-20 years, the synthesis of growth hormone gradually declines. Then the period of stabilization begins, and after 30 years - the stage of decline, which lasts until death. For the age of 60 years, the production of only 40% of the somatotropin norm is typical. Adults need this substance to restore torn ligaments, strengthen joints, and heal broken bones.

Action

Among all pituitary hormones, somatotropin has the highest concentration. It is characterized by a large list of actions that the substance produces on the body. The main properties of growth hormone are:

Acceleration of linear growth in adolescents. The action is to lengthen the tubular bones of the limbs. This is possible only in the prepubertal period. Further growth is not carried out due to endogenous hypersecretion or exogenous influx of GH.
Increased lean muscle mass. It consists in inhibition of protein breakdown and activation of its synthesis. Somatropin inhibits the activity of enzymes that destroy amino acids. It mobilizes them for the processes of gluconeogenesis. This is how the hormone for muscle growth works. It is involved in protein synthesis, enhancing this process, regardless of the transport of amino acids. Works in conjunction with insulin and epidermal growth factor.
Formation of somatomedin in the liver. This is the name of insulin-like growth factor, or IGF-1. It is produced in the liver only under the action of somatotropin. These substances work in conjunction. The growth-stimulating effect of GH is mediated by insulin-like factors.
Reducing the amount of subcutaneous fat. The substance contributes to the mobilization of fat from its own reserves, due to which the concentration of free fatty acids in the plasma increases, which are oxidized in the liver. As a result of the increased breakdown of fats, energy is generated that goes to enhance protein metabolism.
Anti-catabolic, anabolic action. The first effect is the inhibition of the breakdown of muscle tissue. The second action is to stimulate the activity of osteoblasts and activate the formation of the protein matrix of the bone. This leads to muscle growth.
Regulation of carbohydrate metabolism. Here the hormone is an insulin antagonist, i.e. acts opposite to it, inhibiting the use of glucose in tissues.
Immunostimulatory effect. It consists in activating the cells of the immune system.
Modulating effect on the functions of the central nervous system and the brain. According to some studies, this hormone can cross the blood-brain barrier. Its receptors are found in some parts of the brain and spinal cord.

Somatotropin secretion

Most somatotropin is produced by the pituitary gland. The full 50% of the cells are called somatotropes. They produce the hormone. It got its name because the peak of secretion falls on the phase of rapid development in adolescence. The saying that children grow up in their sleep is entirely justified. The reason is that the maximum secretion of the hormone is observed in the first hours of deep sleep.

The basic rate in the blood and peak fluctuations during the day

The normal content of somatropin in the blood is about 1-5 ng / ml. During peak concentrations, the amount rises to 10-20 ng / ml, and sometimes even up to 45 ng / ml. There may be several such jumps during the day. The intervals between them are about 3-5 hours. The most predictable highest peak occurs for a period of 1-2 hours after falling asleep.

Age changes

The highest concentration of somatropin is observed at the stage of 4-6 months of intrauterine development. This is about 100 times more than an adult. Further, the concentration of the substance begins to decrease with age. This happens between the ages of 15 and 20. Then comes the stage when the amount of somatropin remains stable - up to 30 years. Subsequently, the concentration again decreases until old age. At this stage, the frequency and amplitude of secretion peaks decrease. They are maximum in adolescents during intensive development during puberty.

What time is produced

About 85% of somatropin is produced between 12 and 4 in the morning. The remaining 15% is synthesized during daytime sleep. For this reason, for normal development, children and adolescents are advised to go to bed no later than 21-22 hours. Also, don't eat before bed. Food stimulates the release of insulin, which blocks the production of somatropin.

In order for the hormone to benefit the body in the form of weight loss, you need to sleep at least 8 hours a day. It is better to lie down before 23:00, because the largest amount of somatropin is produced from 23:00 to 2:00 in the morning. Immediately after waking up, you should not have breakfast, because the body still continues to burn fat due to the synthesized polypeptide. It is better to postpone the morning meal for 30-60 minutes.

Secretion regulation

The main regulators of somatotropin production are the peptide hormones of the hypothalamus - somatoliberin and somatostatin. Neurosecretory cells synthesize them into the portal veins of the pituitary gland, which directly affects somatotropes. The hormone is produced due to somatoliberin. Somatostatin, on the contrary, suppresses the secretion process. Somatropin synthesis is influenced by several different factors. Some of them increase the concentration, while others, on the contrary, decrease it.

What factors contribute to the synthesis

It is possible to increase the production of somatropin without the use of medications. There are a number of factors that contribute to the natural synthesis of this substance. These include the following:

thyroid loads;

estrogens;

ghrelin;

full sleep;

hypoglycemia;

somatoliberin;

amino acids - ornithine, glutamine, arginine, lysine.

Factors causing deficiency

Secretion is also affected by some xenobiotics, chemicals that are not part of the biotic cycle. Other factors that lead to hormone deficiency are:

hyperglycemia;
somatostatin;
high blood levels of free fatty acids;
increased concentration of insulin-like growth factor and somatotropin (most of it is associated with a transport protein);
glucocorticoids (hormones of the adrenal cortex).

What causes an excess of somatotropic hormone

If in adults the level of somatropin is equal to the concentration that is characteristic of a growing organism, then this is considered an excess of this hormone. This condition can lead to serious health problems. These include:

Acromegaly and gigantism. The first concept is an increase in the size of the tongue, a strong thickening of the bones and coarsening of facial features. Gigantism is characteristic of children and adolescents. The disease is manifested by a very large growth, a proportional increase in bones, organs, soft tissues. In women, this figure can reach 190 cm, and in men - 200 cm. Against this background, small head sizes, an increase in the size of internal organs and lengthening of the limbs are noted.
tunnel syndrome. Pathology is a numbness of the fingers and hands, accompanied by tingling pain in the joints. Symptoms appear due to compression of the nerve trunk.
tissue insulin resistance. This is the name of the violation of the biological response of body tissues to the action of insulin. As a result, sugar cannot pass from the blood into the cells. Because of this, the concentration of insulin is constantly at a high level, which leads to obesity. The result is that you can’t lose weight even on a strict diet. All this is accompanied by hypertension and edema. Insulin resistance increases the risk of cancer, type 1 diabetes, heart attacks, atherosclerosis, and even sudden death due to blockage of blood vessels.

The consequences of a lack of growth hormone

For the human body, not only an excess of somatropin is catastrophic, but also a deficiency. A deficiency of this substance leads to a weakening of emotional reactions, a decrease in vitality, increased irritability and even depression. Other consequences of somatropin deficiency are:

Pituitary dwarfism. This is an endocrine disease, which is a violation of the synthesis of somatropin. This condition causes a delay in the development of internal organs, the skeleton. Mutations in the GH receptor gene are manifested by abnormally short stature: in men it is about 130 cm, and in women it is less than 120 cm.
Delayed physical and mental development. This pathology is observed in children and adolescents. In 8.5% of them, short stature is observed due to a lack of somatropin.
Delayed puberty. With this pathology, there is an underdevelopment of secondary sexual characteristics in comparison with most other adolescents. Delayed puberty is caused by a slowdown in overall physical development.
Obesity and atherosclerosis. In violation of the synthesis of somatropin, a failure of all types of metabolism is observed. This is what causes obesity. Against this background, a large amount of free fatty acids is observed in the vessels, which can cause their blockage, which will lead to atherosclerosis.

How is somatotropin used?

This substance can also be synthesized artificially. In the very first production experiment, an extract of the human pituitary gland was used. Somatropin until 1985 was extracted from human corpses, so it was called cadaveric. Today, scientists have learned how to synthesize it artificially. In this case, the possibility of infection with Creutzfeldt-Jakob disease is excluded, which was possible when using a cadaveric preparation of GR. This disease is a fatal pathology of the brain.

The FDA-approved drug based on somatropin is called Somatrem (Protropin). Therapeutic use of this remedy:

treatment of nervous disorders;
accelerating the growth of children;
fat loss and muscle building;

Another area of use of Somatrem is the prevention of senile diseases. In older people, GH leads to an increase in bone density, increased mineralization, a decrease in adipose tissue and an increase in muscle mass. In addition, they have a rejuvenation effect: the skin becomes more elastic, wrinkles are smoothed out. The downside is the manifestation of several adverse reactions, such as arterial hypertension and hyperglycemia.

In the treatment of nervous disorders

Somatropin improves memory and cognitive functions. This is especially necessary for patients with pituitary dwarfism. As a result, a patient with a low content of somatotropin in the blood improves well-being and mood. An increased level of this substance is also not recommended, because it can cause the opposite effect and cause depression.

With pituitary dwarfism

Treatment of developmental disorders in children is possible through stimulation by daily administration of pituitary extract. It affects not only one gland, but also the body as a whole. It is worth using such injections as early as possible and until the end of puberty. To date, a course of growth hormone is the only effective way to treat pituitary dwarfism.

Peptides in bodybuilding

The effect of burning fat and increasing muscle mass is especially often used by professional bodybuilders during active training. Athletes take peptides for muscle growth in combination with testosterone and other drugs with a similar effect. The use of Somatrem was banned in 1989 by the International Olympic Committee, but this did not rule out the illegal use of this drug. In combination with GH, bodybuilders use the following drugs:

Steroids. Their powerful anabolic action enhances the hypertrophy of muscle cells, which accelerates their development.
Insulin. It is necessary to relieve the burden on the pancreas, which, due to an increase in the level of GH, begins to work too actively and depletes its reserves.
Thyroid hormones of the thyroid gland. In a small dose, they exhibit an anabolic effect. Taking thyroid hormones speeds up metabolism and accelerates tissue growth.

How to Increase Growth Hormone Production

There are different growth hormone stimulants. One of them is taking certain medications. Although natural methods also help to increase the production of somatropin. For example, in people who exercise regularly, the effects of IGF-1 and GH are enhanced. This was not observed in untrained subjects. Somatropin synthesis also occurs throughout sleep, so it is very important that a person sleeps normally. The intake of multivitamin complexes helps to increase the amount of GH produced, including:

minerals;
vitamins;
amino acids;
natural adaptogens;
substances of plant origin - chrysin, forskolin, griffonia.

Somatotropin tablets

Even though the substance is officially banned in sports, the temptation to use it is very high. For this reason, many athletes still resort to this method to remove excess adipose tissue, tighten their figure and gain more relief. The advantage of its use is the strengthening of bones. If the athlete is injured, which happens very rarely, then taking somatropin accelerates healing. The drug has a number of side effects, such as:

increased fatigue and loss of strength;
development of scoliosis;
pancreatitis - inflammation of the pancreas;
loss of clarity of vision;
accelerated muscle development and compression of peripheral nerves;
bouts of nausea and vomiting;
joint pain.

Even with the positive effects of the drug, some people should not use it. Contraindications include the following pathologies:

allergy to the components of the drug;
malignant tumors;
a threat to life in the form of a postoperative period and acute respiratory failure;
pregnancy and lactation.

Caution must be observed in hypothyroidism, hypertension and diabetes mellitus. It is important at the time of taking growth hormone to give up alcohol. Disputes about the dangers of using this substance are still going on. According to some experts, the risk of use is limited to an increase in the amount of glucose in the blood and the appearance of swelling. Although there have been cases of an increase in the size of the liver and even legs, this only applies to cases of exceeding the dosage.

What products contain

No less important for increasing the production of somatotropin is proper nutrition. It must be balanced. It is recommended to give preference to lean foods, because fatty foods cause a decrease in GH. The list of foods that include protein and other substances necessary for recuperation and raising the level of somatotropin includes:

cottage cheese;
chicken eggs;
buckwheat and oatmeal;
veal;
legumes;
milk;
poultry meat;
nuts;
fish;
lean beef;

Physical activity

Almost any motor activity has a positive effect on the secretion of somatropin. It can be regular walking or weightlifting. Although some types of loads are more efficient. Sports divide them into two groups - power (anaerobic) and aerobic (cardio). The first group includes heavy lifting for a short time. Aerobic exercise includes walking, running, skiing, cycling, etc. To increase the production of GR, it is necessary to reasonably combine these two types of exercise. The most useful are:

weight training with a number of repetitions from 10 to 15;
walking at an approximate speed of 4-6 km / h.

A complete night's sleep

For the synthesis of somatropin, a full sleep for 8 hours is necessary. Natural production begins 1.5-2 hours after falling asleep. This is the deep sleep phase. When a person does not have the opportunity to spend the allotted time sleeping at night, then it is imperative to rest at least 1-2 hours during the day. Even regular exercise and a healthy diet with lack of sleep will not give the desired result.

Video

Did you find an error in the text?
Select it, press Ctrl + Enter and we'll fix it!