Chapter 6. Hormonal system

A biological organism is an integral system of closely related organs, regardless of physical proximity, which can function correctly only if feedback systems are working.The most significant system of control and communication between various organs and systems is, of course, the endocrine system, which can be positioned as a kind of supra-systemic complex that bears most of the responsibilities for compensatory and adaptive reactions.

By itself, in autonomous mode, the heart has no idea that the body is in a state of stress or danger, and therefore does not know that it is vital to increase the rate of contraction of the heart muscle and increase blood pressure in order to provide the organs with a sufficient level of blood flow.The lungs cannot autonomously respond to the fact that a person is running, which means that the excursion (movement of the diaphragm during breathing) of the diaphragm should increase, and the rate of blood saturation with oxygen in the alveoli should increase.And the nervous system “does not know” what is happening in the body and what processes need to be strengthened in order to increase a person’s chances of survival.All this is achieved through constant signaling, mainly through the action of hormones.

The endocrine system consists of a number of endocrine glands, that is, organs that synthesize and release hormones into the blood.The endocrine system includes the pituitary gland, thyroid and parathyroid glands, pancreas, adrenal glands and gonads, which are specifically interconnected.Organs and tissues that are not related to the endocrine system, such as adipose tissue, intestines, stomach and others, can produce hormones, but their contribution to the overall control function is somewhat less.

Hypothalamic-pituitary axis

The central mechanism of humoral regulation is, of course, the so-called hypothalamic-pituitary axis, which includes key control structures - the hypothalamus and pituitary gland.This axis does not function in isolation; it always has a third component - the target organ, the endocrine gland, whose activity is, in fact, regulated.This is how the axes “hypothalamus – pituitary gland – adrenal glands”, “hypothalamus – pituitary gland – gonads”, “hypothalamus – pituitary gland – thyroid gland” are formed.In addition to its controlling function, each structure of the axis also produces substances that have systemic effects on the entire body.

Hypothalamus

The hypothalamus is one of the most important structures of the central nervous system, playing a controlling and regulatory role.This relatively small area in the diencephalon includes many groups of cells united into nuclei that influence the neuroendocrine system functioning in the brain and the constancy of the internal environment of the body, homeostasis in general.

In simple terms, we can distinguish two major areas of work of the hypothalamus - control of a number of functions of the brain itself and its interaction with the pituitary gland through the synthesis of substances that stimulate the pituitary gland for further synthesis of hormones - the production of so-called releasing factors, or liberins, and, depending on the current situation in the body, inhibitory factors (statins), which reduce the production of tropic hormones by the pituitary gland.

The activity of the hypothalamus is not chaotic, but clearly dependent on the needs of the body and aimed at ensuring survival.Thus, by directly receiving information about the biochemical composition of blood and cerebrospinal fluid, the content of specific substances in them, temperature, etc., the hypothalamus directly controls the feeling of thirst, hunger, maintains the required temperature and the cycle of sleep and wakefulness, participates in the formation of sexual behavior and many other behavioral patterns related to higher cortical functions (emotional state, empathy, memory).

In addition, the hypothalamus is connected through nerve pathways to almost all structures of the brain, becoming the cornerstone of the interaction between neural and humoral control mechanisms.

Pituitary gland

The pituitary gland, also known as the pituitary gland, is a central regulatory humoral organ that produces hormones that control growth, metabolism in general, and reproductive function.Structurally, the pituitary gland consists of two large parts, different in origin: the anterior lobe, the adenohypophysis, which makes up up to 80% of the organ, and a smaller part, the posterior lobe, the neurohypophysis.Between them, a person has a thin layer - the intermediate lobe.

The adenohypophysis synthesizes so-called tropic hormones that directly control the activity of target organs.Thus, thyroid-stimulating hormone (TSH) controls the biosynthesis and secretion of thyroid hormones, adrenocorticotropic hormone (ACTH) controls the function of the adrenal glands, gonadotropic hormones (follicle-stimulating and luteinizing hormones) control the activity of the gonads, somatropic hormone (STH) controls protein synthesis, prolactin controls lactation, the formation of a number of behavioral patterns associated withcare for the offspring, and also participates in the control of cell differentiation and metabolism.

In the posterior lobe of the pituitary gland, a number of active substances are deposited and secreted into the blood, the most important of which are vasopressin and oxytocin.

A number of specific hormones are formed in the intermediate lobe, in particular melanocyte-stimulating hormones, etc.

If the target organ, for one reason or another, produces few hormones, as a result of the action of the hormonal axis, a tropic hormone is produced, which stimulates the organ to work more intensively.At the moment when the production of hormones in the target organ is optimized, the synthesis of tropic hormone decreases.This is how the constancy of the hormonal activity of peripheral endocrine organs is regulated on an ongoing basis.

Thyroid and parathyroid glands

The thyroid gland is one of the key human endocrine organs, which produces, under the control of the pituitary gland (under the influence of thyroid-stimulating hormone), iodine-containing hormones, which are of great importance for human metabolism, growth, development and adaptive processes.

The main thyroid hormones are thyroxine and triiodothyronine, which are produced in special cells of the thyroid gland - thyrocytes.In other cells - parafollicular, C-cells, other active substances are synthesized - peptide hormone, calcitonin, which regulate the exchange of calcium and phosphates in bone tissue.In patients with reduced thyroid function, metabolic processes, healing and regeneration noticeably slow down, and inevitable changes occur in the immune, hormonal and nervous systems.The most significant changes in the function of the thyroid gland are in childhood, since a hypofunctional state and deficiency of thyroid hormones lead to delays in psychomotor and psycho-speech development.Even 20 years ago, the main cause of hypofunction of the thyroid gland was deficiency of iodine and a number of essential microelements, but modern hypothyroidism is increasingly of an autoimmune nature.

When the production of thyroid hormones decreases, by feedback principle, the hypothalamic-pituitary axis “starts up” and begins to stimulate the peripheral organ by producing thyroid-stimulating hormone (TSH).If the thyroid gland makes up for the deficiency, the secretion of thyroid-stimulating hormone stops.Thus, by the ratio of the amount of thyroid hormones, tropic hormone, detection of autoantibodies to the thyroid gland (AT to TSH, AT to TG, AT to TPO), as well as by identifying chronic foci of infection and deficiency conditions, it is possible to correct the process of hormone production.

The thyroid gland is not always in a state of reduced function; there are also conditions accompanied by excessive secretion of hormones.This condition is called hyperthyroidism and thyrotoxicosis and can reach such a pronounced degree that it begins to threaten the body as a whole.With hyperthyroidism, metabolism is excessively accelerated, autonomic and vascular reactions to increased amounts of hormones occur (tachycardia, increased breathing, feelings of hot flashes and heat, anxiety, sleep disturbances, weight loss, etc.).Hyperthyroid conditions may also be associated with disruption of axis feedback, and especially with autoimmune inflammation.

It should be noted that the thyroid gland does not function in isolation; its biochemical processes are finely integrated in interaction with the adrenal glands (the “thyroid gland - adrenal glands” axis).Within this system, both thyroid pathology can lead to adrenal fatigue, and adrenal dysfunction over time inevitably leads to thyroid pathology.The main common points of influence of the thyroid gland and adrenal glands are the regulation of metabolism in general, the stability of cognitive and psycho-emotional status.

Adrenal glands

The adrenal glands are key peripheral endocrine organs that systemically regulate the entire metabolism in the human body, its ability to grow, develop, as well as the systemic response to provoking factors and adaptation.

Anatomically, the adrenal gland consists of several structures, the cortex and the medulla, each of which produces a spectrum of hormones that have their own biological significance.

The adrenal cortex consists of three zones - glomerular (aldosterone, corticosterone, deoxycorticosterone), fascicular (cortisol and cortisone) and reticular (sex hormones).Hormones of the first zone belong to the group of mineralcorticoids, hormones that affect water-salt metabolism and regulate electrolyte balance.Hormones of the zona fasciculata - glucocorticosteroids - are key hormones of adaptation to stress and modulation of the immune system.

Cells of the adrenal medulla synthesize catecholamines - adrenaline and norepinephrine, as well as a number of regulatory peptides.All adrenal hormones are of great importance for the regulation of biological processes in the body, but the ratio and proper regulation of the production of these hormones is no less important.

The abundance of hormones produced in the adrenal glands makes this seemingly small paired organ the center of all humoral regulation.Modern endocrinology, both pediatric and adult, undeservedly downplays the importance of the adrenal glands, despite the fact that it is not possible to consider the problems of the immune system, growth, development, maturation of a child and then an adolescent, the psycho-emotional and cognitive state of an adult, the mental and cognitive status of the elderly without assessing and timely correction of hormonal status.

The problems of modern endocrinology are aggravated by the lack of reference values for children and adolescents, and a number of laboratories refuse to accept samples if the patient has not reached the age of 18, explaining this by the lack of expediency of such research, despite the fact that it is the adrenal glands in the pre-pubertal period that bear the key responsibility for physical and mental development, in contrast to the adult body, in which hormonal well-being is achieved through the functioning gonads, and the “adrenal glands -” axis.gonads" has a significantly greater compensatory resource, which means more opportunities to achieve hormonal balance.In a child’s body, the adrenal glands work outside of this axis and experience, in fact, double load.

Adrenal hormones determine the maturation and functioning of all organs and systems, including the central nervous system.The window of formation, growth and maturation of organs is significantly limited in time and has age limits, for example, the possibilities for the growth of tubular bones are limited to the age of 18–20 years in boys, 18 years in girls, the growth of the penis, both in length and in diameter, is limited to the age of 16–17 years.Timely corrected hormonal deficiency allows you to maintain the health of the young body and ensure its reproductive realization in the future.Late attempts at correction, even with the use of active hormone replacement therapy in adulthood, cannot activate the growth of hormone-dependent organs.And behavioral scenarios formed against the background of hormonal dysfunction can determine psychosocial functioning throughout life.

Pancreas

The pancreas is a unique organ in the human body that has both exocrine, that is, exocrine, and intrasecretory, that is, endocrine, functions.The external secretion of the pancreas is responsible for the production of the most important food enzymes (amylase, lipase, protease, maltase, etc.).The synthesized enzymes are released into the lumen of the duodenum.The ability of exocrine secretion makes the pancreas one of the key organs of the gastrointestinal tract, on which the digestion of fatty foods depends (pancreatic lipase together with bile contribute to the breakdown of fats in the intestinal lumen into fatty acids; alpha-amylase breaks down carbohydrates, protease – food protein).

However, the functional activity of the organ does not end there; in its structure there are so-called “pancreatic islets”, which belong to endocrine structures, that is, they produce and release hormones into the blood.The hormones of the pancreas include glucagon (a hormone that increases the level of glucose in the blood), insulin (the main hypoglycemic hormone that promotes the transfer of glucose from the blood into the cell, due to which the level of glucose in the blood decreases), ghrelin (a hormone that stimulates appetite), somatostatin (a modulator of the glands).The main importance of pancreatic hormones is the control of carbohydrate metabolism through the production of glucagon and insulin.

Damage to the pancreas leads to a decrease in both functional components - both exo- and endocrine work.A chronic and autoimmune process of the pancreas leads to severe metabolic disorders in general, especially carbohydrate metabolism.Due to the close interconnections of all parts of metabolism, its disruption leads to the development of interrelated systemic pathological conditions (for example, metabolic syndrome and diabetes mellitus).

Sex glands

The gonads are key paired organs responsible for reproductive function and generally carry endocrine activity, affecting metabolism in the human body.The gonads are characterized by mixed secretion; they simultaneously secrete germ cells (eggs or sperm) and release hormones into the blood - androgens and estrogens.The functioning of the gonads depends on the control of tropic hormones of the pituitary gland, which, in turn, are controlled by hypothalamic factors.

The main gonadotropic hormones of the pituitary gland are follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

The main sex hormones that are detected in both men and women are testosterone, estradiol and progesterone.These hormones and their ratio determine not only the physical formation at puberty, sexual desire and behavior, the menstrual cycle, the type of hair growth, but also have a number of systemic effects on the immune system, connective tissue and nervous system.

Key hormones

Oxytocin

Oxytocin is a neuropeptide that is synthesized in the hypothalamus and accumulates in the posterior lobe of the pituitary gland.It has a number of vital effects in the biological organism, affecting muscle tone, adrenal function, reproductive function and neurotransmitter metabolism, due to which important social and behavioral phenomena are realized.

The largest amount of oxytocin is produced in a woman’s body after the birth of a child, due to which that very strong empathic connection between the newborn and the mother is formed, which, based on the most seemingly unobvious signs, begins to determine what exactly the child needs and what worries him.This biochemical phenomenon in nature allows the baby to survive, and in human life - to form the mother’s attachment necessary for the baby’s development.

Oxytocin is produced not only in women and not only during the newborn period of a child, it is synthesized throughout a person’s life and determines his psycho-emotional state and so-called empathy - the ability to read and understand the feelings of another person without words.

Oxytocin promotes feelings of satisfaction, calm, and reduced anxiety through its effects on areas of the brain responsible for behavioral stress responses.In addition, oxytocin acts as an antagonist of stress hormones produced by the adrenal glands.

The synthesis of your own oxytocin is stimulated in different ways, but the simplest ways are tactile contact, tight hugs, and irritation of erogenous zones, especially the nipples.

Deficiency of oxytocin production in adults and children with high levels of stress leads to a number of psycho-emotional changes, such as anxiety, internal tension, panic attacks, and impaired socialization.

In case of oxytocin deficiency in a woman who has given birth, the risk of bleeding increases sharply, since it is under its influence that the smooth muscles of the uterus contract.

In such cases, the oxytocin deficiency is replenished externally by administration intramuscularly (mainly for young mothers), intramuscularly (into the nose), sublingually (under the tongue) or inhalation.

When oxytocin is administered into the nose, rapid and effective penetration through the blood-brain barrier is achieved and it is delivered to the nervous system, where it has effects similar to endogenous ones.

Oxytocin is used throughout the world as part of complex treatments for behavioral disorders, social interaction disorders, attention deficit disorders, eating disorders, libido and reproductive disorders.

Corticotropin

Adrenocorticotropic hormone is one of the key hormones for metabolism, synthesized in the pituitary gland from a protein - the precursor of pro-opiomelanocortin, from which beta-endorphin, melanocyte-stimulating hormone and lipotropin are also synthesized.The synthesis of corticotropin is subject to the rhythm of the release of corticoliberin, a releasing factor of the hypothalamus.The maximum secretion of corticoliberin, and, accordingly, corticotropin and adrenal hormones, occurs from five to seven in the morning, and the minimum - from six to eleven in the evening.

Starting from three in the morning, the secretion of releasing factor begins to increase, gradually preparing the human body for awakening, while the evening decline in corticotropin and corticotropin allows the hormonal status to balance and go into deep sleep.

Corticotropin interacts with specific melanocortin receptors, which are located primarily on cells of the adrenal cortex, as well as in adipose tissue, but ACTH can interact with melanocortin receptors of the immune system, skin and melanocytes.

In the adrenal glands, ACTH is responsible for the synthesis and secretion of hormones mainly from the zona fasciculata - glucocorticosteroids (cortisol, cortisone, corticosterone), increases the production of progesterone, androgens and estrogens;Corticotropin also increases the sensitivity of peripheral tissues to the listed hormones.

Glucocorticoids have a key effect on metabolism, stimulating the synthesis of glucose and fats, suppressing the activity of the immune system, inhibiting the synthesis of connective tissue, and also affecting the nervous system, increasing its excitability.

Through the production of corticotropin, the production of mineralcorticoids, primarily deoxycorticosterone and aldosterone, is stimulated, but another control system is of greater importance in controlling the metabolism of mineralcorticoids - the so-called renin-antiotensin-aldosterone system, which plays a key role in the regulation of blood pressure and circulating blood volume in the body.

Another indirect effect of corticotropin is the stimulation of catecholamine production in the adrenal medulla.Despite the fact that the main control of catecholamine metabolism falls on the sympathetic stimulation of chromaffin cells, as well as the chromaffin tissue itself, which responds to changes in blood composition.

The interaction of corticotropin with other peptide hormones, primarily prolactin, vasopressin and opioid peptides, as well as the relationship with the monoamine system of the hypothalamus, which affects memory, motivation and learning, is also important.

Somatotropin

Somatotropin is a somatotropic hormone - one of the hormones of the anterior pituitary gland, which is often called “growth hormone” for its effect on the development of tubular bones and human growth.However, this action is far from the only and not the most significant.Somatotropic hormone significantly accelerates the processes of all plastic metabolism (anabolism) and has a powerful anti-catabolic effect (stopping decay processes).

Endogenous somatotropin is produced in the pituitary gland under the influence of hypothalamic somatotropin, but it is also stimulated by other influences, both physical and humoral.STH increases under the influence of ghrelin (the hunger hormone produced by the pancreas), estrogens, glucocorticosteroids, and thyroid hormones.Increased secretion of GH occurs during physical activity, a decrease in glucose levels, and maximum synthesis at a young age occurs at night, which is why the saying “children grow in their sleep” was born.

Somatropin significantly affects all components of metabolism, enhancing protein synthesis, increasing the concentration of glucose in the blood and enhancing fat catabolism.GH has a significant effect on the immune system, stimulating its functions.

Somatotropin carries out most of its functions directly, but part of its effects are carried out through insulin-like growth factors, primarily IGF-1 (somatomedin C).Endogenous IGF-1 is predominantly synthesized in the liver under the influence of growth hormone and stimulates the development of internal organs.Due to IGF-1, feedback is provided with the hypothalamus and pituitary gland, since with its significant increase in the blood, somatostatin is produced - this ensures control of hormonal status.

The level of insulin-like factor-1 depends not only on the concentration of growth hormone, but also on sex steroids, thyroid hormones, glucocorticosteroids and insulin, while insulin and sex hormones stimulate the production of IGF-1, and glucocorticosteroids largely inhibit.

Thus, insulin, growth hormone, thyroid hormones and sex hormones are in synergism regarding growth and development, promoting synthesis processes.In order for somatotropin to exhibit its anabolic capabilities, a sufficient amount of insulin is necessary, since, unlike carbohydrate metabolism, where growth hormone and insulin are antagonists, in relation to protein synthesis they act together and reinforce each other.

In addition to the importance of GH in childhood and adolescence, its importance in the prevention of the development of diseases of old age and anti-aging medicine in general has been discussed for many years.A number of studies have shown that with a decrease in IGF-1 and growth hormone, as well as with impaired cell sensitivity to them, life expectancy decreases.

At a young age, somatotropin primarily determines the processes of growth and development of the child as a whole due to systemic activation of the musculoskeletal system, myelination and maturation of the brain, support of detoxification systems and increased membrane density and increased efficiency of the adrenal glands.

In the case of severe injuries to the brain and spinal cord, damage to internal organs, or simply long-term diseases that require large energy expenditures by the body, additional GH subsidies become a key trigger for regeneration.In our clinical practice, we use the full range of growth factors and releasing factors.

Luteinizing (LH) and follicle-stimulating (FSH) hormones

Luteinizing and follicle-stimulating (gonadotropic) hormones are peptide molecules synthesized in the anterior pituitary gland under the influence of the hypothalamic releasing factor.

In women, follicle-stimulating hormone determines the preparation and growth of the follicle in the ovary, preparing it for the effects of luteinizing hormone.In men, follicle-stimulating hormone affects the development of seminiferous tubules, enhances the secretion of testosterone and induces the formation and then maturation of sperm.After puberty, the concentration of follicle-stimulating hormone in men remains constant, while in the female body the cyclical production of FSH and LH will remain until menopause.

Luteinizing hormone is vital for the normal functioning of the reproductive system, stimulating the secretion of estrogen in the female body and, at its peak, ovulation, and in the male body directly stimulating the secretion of testosterone by interstitial Leydig cells in the testes.The higher the LH level in a man’s blood, the more intense the production of testosterone.

When the concentration of sex hormones decreases, the synthesis and secretion of luteinizing and follicle-stimulating hormones is stimulated, and a high concentration inhibits them.

In childhood, FSH rises briefly immediately after birth and decreases significantly at 6 months in boys and by a year or two in girls, then the concentration of FSH increases before the onset of puberty and accompanies the formation of sexual characteristics.It is worth noting that the rise in FSH concentration at night is one of the first laboratory signs of puberty; the level of gonadal hormones also increases at the same time.

Pregnenolone

One of the key neurosteroids is pregnenolone, a precursor of steroid hormones, which is synthesized in various steroidogenic tissues and organs, especially in the adrenal glands and the central nervous system.

For a long time, pregnenolone was considered an inactive steroid with no biological function other than serving as a precursor to other steroid hormones.However, its anti-inflammatory and anti-fatigue properties were recognized as early as the 1930s.

It has anti-inflammatory effects, maintaining immune homeostasis in various inflammatory conditions.Pregnenolone and its metabolic derivatives have been shown to have beneficial effects on the brain, including improving memory and learning, correction of depressive disorders and modulation of cognitive functions.A number of studies have observed decreased levels of pregnenolone in neuroinflammatory diseases, highlighting its role in neuroprotection and neuroregeneration.Pregnenolone and its metabolites play a neuroprotective role in various neuroinflammatory diseases, including Alzheimer's disease (AD) and multiple sclerosis (MS), as well as neuropsychiatric disorders such as schizophrenia, depression and autism.

The mechanism of action of pregnenolone has been studied over the past decades, and new scientific works confirm the expansion of the range of its capabilities.

In men and women, pregnenolone produced in the adrenal glands has a high chance of being converted to DHEA (dehydroepiandrosterone) or cortisol.In men, pregnenolone produced in the testicles has a high chance of being converted to testosterone, and pregnenolone produced in women's ovaries is likely to be converted to estrogen.

Progesterone

Progesterone is a steroid hormone produced by the gonads, adrenal glands, brain and placenta during pregnancy.Progesterone is the most important regulator of normal human reproductive function, and is also characterized by non-reproductive functions relating to the bone, central nervous and immune systems.Progesterone also affects the exchange of water and electrolytes, lipids, carbohydrates, and proteins.As a steroid hormone, progesterone realizes its functions by binding to intracellular receptors, which are ligand-activated transcription factors.In addition to slow-onset genomic effects, progesterone can induce rapid non-genomic cellular responses by binding to plasma membrane receptors, activating various intracellular cascades and second messengers.

During pregnancy, progesterone is involved in the processes of ovulation and implantation, the transformation of the endometrium into decidual tissue, inhibition of uterine contractility, suppression of the mother's immune system, growth and development of the mammary glands, and development of fetal tissue.

Some functions of progesterone include stimulation of glucogenesis, stimulation of mitochondrial energy metabolism, cyclic nucleotide metabolism, protein synthesis and secretion.Progesterone can also reduce the level of lipid peroxidation in cells and reduce cell damage from free radicals.

Progesterone has functional effects on a wide range of immune mechanisms, affecting various subtypes of cells expressing progesterone receptors, including monocytes, macrophages, dendritic cells and lymphocytes.Progesterone acts on the immune system through various signaling pathways, including changes in the transcription of cytokine genes, changes in ion transport (blocking Ca

Progesterone is a neuroactive steroid.The concentration of progesterone in the central nervous system is determined by hormones produced by peripheral glands that cross the blood-brain barrier and by the autonomous production of progesterone by neurons and glial cells.Progesterone in the central nervous system has neuroprotective and neurotrophic effects, and also regulates mood and cognitive function.The neuroprotective effect of progesterone is associated with several mechanisms: by attenuating lipid peroxidation and destruction of cell membranes by free radicals, by modulating the activity of neurotransmitter receptors, and by regulating the expression of specific genes of neurons and glial cells.

The neurotrophic properties of progesterone are associated with its ability to stimulate myelination and remyelination in both the central nervous system and the peripheral nervous system, acting directly on glial cells and Schwann cells.

Testosterone

Testosterone is a steroid hormone related to androgens, synthesized in the gonads and adrenal cortex.Although testosterone is a male sex hormone, it is the most important androgen in women.In women, approximately 50% of circulating testosterone is produced primarily through peripheral conversion of androstenedione, with the remaining half secreted by the ovaries and adrenal glands.The cellular effects of testosterone can be genomic, associated with gene transcription and translation, and nongenomic, mediated by ionic currents and/or initiation of signal transduction cascades by second messengers.Testosterone can act directly through the androgen pathway or indirectly through conversion to estrogen, serving as a local source of estrogens in the central nervous system.

In adults, testosterone is synthesized in both the gonads and the adrenal glands.In children and adolescents, the value of testosterone is colossal, but there is only one source - the adrenal glands.Given the high incidence of adrenal dysfunction, clinical observations are increasingly identifying children with an absolute deficiency of hormonal status, including absolute testosterone deficiency.

Of course, the main function of testosterone is to regulate sexual differentiation, maturation and functioning of the reproductive function of men.Testosterone regulates sexual behavior and sexual desire, determining gender identification.No less significant is the systemic effect of testosterone – its effect on metabolism.Testosterone has a powerful anabolic effect - it promotes protein formation and increases muscle and bone mass.Testosterone can also be called one of the most powerful stimulators of collagen formation, the main structure of connective tissue.In conditions of deficiency of collagen formation, decay processes begin to prevail, which leads to dysplastic and degenerative changes in connective tissue structures.

The effect of testosterone on carbohydrate metabolism is also important.Testosterone not only affects blood glucose levels, but fundamentally determines the key mechanisms of intracellular signaling in the beta cells of the pancreas, which synthesize insulin.Modern research shows that testosterone deficiency in men significantly increases the risk of developing type 2 diabetes.Testosterone is also characterized by a stimulating effect on erythropoiesis.

Testosterone has a suppressive effect on the immune system, affecting many of its branches.Testosterone suppresses dendritic cell activation by inhibiting the production of cytokines and their ability to induce an immune response.At the same time, testosterone increases the production of reactive oxygen species by macrophages and also enhances the migration of neutrophils.

Testosterone affects the development of the central nervous system and is critical for sexual differentiation of the structure and functions of the brain, causing masculinization and defeminization of sexual behavior, and changes the morphology and function of the central nervous system.In the postnatal period, androgens also have an effect on the central nervous system, being a neurosteroid that can be synthesized directly in the central nervous system and plays an important role in the viability, function and plasticity of neurons.Androgens are also characterized by increased neurogenesis in adulthood.Testosterone stimulates the differentiation of neurons, thereby maintaining their plasticity, promoting synaptic density, and also stimulating neurite outgrowth.

Testosterone is characterized by neuroprotective and neurotrophic properties that contribute to the structural and functional restoration of the nervous system.Testosterone, through conversion to estrogens, provides neuroprotection against glutamate-induced neurotoxicity.Testosterone also plays a critical role in the processes of myelination and remyelination by oligodendrocytes.Testosterone improves the survival of human neurons and astrocytes by acting directly on the mitochondrial membrane, inhibiting the production of reactive oxygen and nitrogen species.

The neuroprotective properties of testosterone significantly relate to the hormonal status in general, behavioral and cognitive properties of a person.Aging and chronic diseases, largely due to disruption of the synthesis and production of sex hormones, lead to disruptions in the functioning of the nervous system.Testosterone is one of the key neurosteroids that determines the formation of behavioral patterns, especially in the formation of a motivational profile and volitional potential, as well as a person’s self-presentation in society.

Social self-presentation refers to the gender presentation that a person begins to demonstrate in early childhood, from one to three years, that is, long before puberty and any sexual identification.So, after a year, a girl begins to “shoot with her eyes,” choose outfits for herself and spin in front of the mirror, and her favorite toys are more likely to be dolls and strollers than cars and soldiers.At the same time, the role of education and example in the family is significantly exaggerated.The behavior of a boy is built in a similar way, who will choose pistols and cars from the proposed set of toys, and his role-playing games will have a masculine character.

In recent years, there have been tendencies to explain the growing feminization of boys, young men and even men by their sphere of activity, upbringing in single-parent families, mainly under the influence of mother and grandmother, as well as a general cultural shift and environmental influence.In our opinion, the proposed argument is untenable.

The role of educator at all times was predominantly assigned to women; these were mothers, grandmothers, nannies, and governesses.The composition of these participants in the educational process has not changed conceptually.

With the beginning of attending a school institution, that is, the process of immersion and adaptation in a society of different ages, it is he who begins to play a key role in the self-identification and development of the child’s personality.From this moment on, the role of the family is relegated to the background, and from adolescence, the child already lives, in fact, an independent social life, has his own formed range of interests, which the family environment can influence very limitedly, and in some cases cannot at all.On the contrary, a delay in this separation, that is, the presence of psychological infantilism, indicates a hormonally dependent delay in the maturation of the nervous system.Domination on the part of an overprotective mother can certainly aggravate the described situation, but does not completely determine it, and excessive psychologization of infantility, lack of independence, and femininity of young men leads to the fact that their hormonal dysfunction remains undiagnosed for years.

The sexual identification of such a young man is only one fragment of the behavioral palette.Other fragments of it are represented by behavioral patterns that are not directly related to sexuality, but that determine social adaptation as a whole.

In most cases, these patterns are defined as conditionally normal: fixation and meticulousness are interpreted as perfectionism and partiality, emotional instability - as “high sensitivity”, requiring a special approach from others, with a request for complete understanding, approval, playing along and praising the “subtle mental organization” of the individual.Each of the described features and characterological traits can be psychologically substantiated, interpreted and explained in such a way as to be within the framework of the conventional “norm”.

However, the totality of all the described traits, including taking into account the psychophysiological and vegetative constitution of a person, reveals a general population shift among men from accentuated masculine behavior towards conditional feminization.A typical illustration of this is the greater participation of men in housekeeping, raising and caring for children, and a decrease in masculine activities (moving away from typically male responsibilities at home).It is worth noting that, unfortunately, this progressive shift is largely supported by the partners of the men described, who willingly shift their feminine responsibilities to their spouses and at the same time expect them to demonstrate truly masculine behavior.A reflection of the current situation can be considered typical scenarios of feature films and theatrical productions, emphasizing the dominant role of a woman in decision-making, providing for the family and the passivity of the role of a man who dutifully follows the direct instructions of his partner.

DGEA

Dehydroepiandrosterone (DHEA) is a steroid hormone synthesized in the zona reticularis of the adrenal cortex from cholesterol or de novo from acetate in response to stimulation of the hypothalamic-pituitary-adrenal axis.In the peripheral blood, the hormone is present predominantly in a sulfated form (DHEAS) and has the highest concentration among all steroids.DHEA is considered as a buffer steroid, which is a precursor for the formation of biologically active sex steroids.DHEA formed in the adrenal glands, entering peripheral tissues, is transformed into biologically active estrogens and testosterone with the help of intracellular enzymatic systems, which carry out their inherent biological effects intracellularly.

In addition to its important role as an autonomous source of the formation of sex steroids, DHEA is an independent multifunctional hormone that affects the functions of the brain, immune system and is involved in the regulation of metabolism.

In terms of their biological action, DHEA and DHEAS are natural antagonists of glucocorticosteroids.Thus, DHEA improves and accelerates the uptake of glucose by cells, reducing tissue resistance to insulin.The effect on lipid metabolism is also important - a decrease in the process of lipogenesis and an increase in lipolysis, increased expression and increased secretion of adiponectin, which helps reduce triglyceride levels.Thus, in general, the effect of DHEA counteracts the development of metabolic syndrome.

Just like testosterone, DHEA stimulates the formation of collagen and prevents its destruction, providing a systemic regenerative effect.The regenerative potential affects not only connective tissue structures, but also all cells of the body, including cardiomyocytes, due to which its cardioprotective effect is described.

DHEA also exhibits an immunoregulatory function, affecting the activity of immune cells and the synthesis of cytokines.

The immunomodulatory properties of DHEA are supported and enhanced by its metabolites.Thus, androstenediol synthesized from DHEA is a modulator of immunological responses to infection and is effective in limiting viral and bacterial infections.

In general, the immunoregulatory effect of DHEA helps stimulate the immune response and reduce inflammation.

In our practice, the central effects of DHEA are actively used, which are realized due to the fact that DHEA and DHEAS are neuroactive steroids, the concentration of which in the central nervous system is 6–8 times higher than their peripheral level.

Circulating peripheral steroids can be taken up into the central nervous system and serve as precursors for the synthesis of neurosteroids produced locally in the hippocampus and other brain structures.DHEA is also directly synthesized de novo and metabolized in the brain.DHEA(S) helps improve memory and cognitive abilities, and also has an antidepressant effect.

The neurobiological effects of DHEA(S) include neuroprotection, neurogenesis and neuronal survival, as well as antioxidant and anti-inflammatory effects through systemic antiglucocorticoid effects.

DHEA(S) promotes neurogenesis and neuronal survival.A possible mechanism for this is an increase in the concentration of brain-derived neurotrophic factor.

DHEA(S) acts as an important component of the stress response, exhibiting potent antiglucocorticoid activity that protects neurons from the neurotoxic effects of corticosterone.In addition to the direct and indirect neuroprotective effect, DHEA affects all neurosteroidogenesis and the synthesis/release of endorphins, and is involved in determining synaptic plasticity, a molecular mechanism underlying cognitive/behavioral functions.

In general, DHEA deficiency manifests itself in reduced resistance to stress, irritability, decreased performance and libido.With complex therapy, these manifestations of acquired adrenal dysfunction are successfully corrected in both adults and children.

Cortisol

Cortisol is the main glucocorticoid hormone of a steroid nature, synthesized in the zona fasciculata of the adrenal cortex from cholesterol under the control of adrenocorticotropic hormone (ACTH) and has a pleiotropic effect.The secretion of cortisol increases when the body is exposed to stressful stimuli of various natures.Cortisol exerts its effect through interaction with intracellular receptors, forming a ligand receptor complex that is transported into the nucleus and affects gene transcription.

Cortisol is involved in all types of metabolism.The effect on carbohydrate metabolism is characterized by stimulation of gluconeogenesis and glycogenase, and cortisol also reduces glucose consumption in peripheral tissues.Cortisol affects fat metabolism by stimulating lipolysis and increasing the oxidation of fatty acids in cells.Thus, cortisol shifts metabolic processes from glucose utilization to fatty acid utilization.Cortisol has a catabolic effect on protein metabolism.

Cortisol plays an important role in regulating the functions of the immune system, affecting quantitative and morphofunctional indicators.Cortisol has a predominantly immunosuppressive and anti-inflammatory effect and is capable of suppressing almost all main components of the immune response.Cortisol regulates the maturation, survival, migration and motility of dendritic cells, and also inhibits their immunogenic functions.

Despite the prevalence of immunosuppressive properties of glucocorticoids, they have a bidirectional effect on the specific functions of effector cells.The effects of cortisol are biphasic and depend on its concentration and time of action.Basal cortisol concentrations support the activity of defense mechanisms and exhibit immunostimulating properties, while higher concentrations caused by stress suppress the immune response.

Corticosteroids are among the hormones with the most important effects on brain function and are associated with effects on mood, stress, anxiety, sleep, appetite, and cognition.The effects of cortisol are mainly reflected in the hippocampus, where the density of receptors for this hormone is especially high, and the prefrontal cortex.The neurobiological effects of glucocorticoids are also biphasic: low doses have a neuroprotective effect, but higher doses increase neurotoxicity, which is associated with different expression of glucocorticoid receptors in brain structures and their saturation.Although small or short-term increases in glucocorticoids associated with stress may have beneficial effects on attention and promote adaptation, higher cortisol levels or long-term increases have detrimental effects on executive function, attention, learning, memory, and cognitive flexibility.

The effects of cortisol on brain structures involved in cognition are associated with changes in responses to serotonin, activation of beta-adrenergic receptors, which contributes to inhibition of the prefrontal cortex.The effect on hippocampal volume may be due in part to changes in brain-derived neurotrophic factor expression in the hippocampus.Also, the adverse effects of stress on the hippocampus are due to glutamatergic mechanisms and are also associated with mitochondrial damage.Another important brain structure that is affected by elevated cortisol levels is the amygdala, which is involved in the implementation of behavioral reactions associated with responding to danger.With chronic stress, hyperactivation of the amygdala generates constant anxiety and contributes to the development of depression.

Also, through nongenomic mechanisms, cortisol influences the activity of several neurotransmitter systems, affecting circuits associated with reward processing, attention regulation, executive function, mood, and emotion.

Key syndromes of hormonal dysfunction

Congenital and acquired adrenal dysfunction

As was said in previous chapters, an increase in the amount of hormonal dysfunction is one of the main pathogenetic links in the development of both personal and population generational degeneration.As our clinical practice shows, many modern children born have a clinically significant decrease in the level of steroid hormones, but this problem has not yet received due attention from specialists.But taking into account clinical and laboratory data, as well as the age of the child, the described changes should be considered as a variant of congenital dysfunction of the adrenal cortex.

The adrenal glands in a child are the most important endocrine organ that determines physical and motor development, bone and ligament density, muscle tone, the state and reactivity of the immune system, as well as the rate of psycho-speech development and psycho-emotional status of the child.Often this hormonal syndrome occurs under the guise of neurological symptoms in the form of decreased resistance to stress, behavioral disorders such as tantrums, hyperactivity, unmotivated aggression or, on the contrary, decreased motivation and will, narrowed range of interests and impaired socialization.

Thus, children with adrenal dysfunction may experience hysterical attacks in response to insignificant situations, especially in noisy, crowded and unfamiliar places.Adaptation difficulties develop according to the same mechanism as panic attacks in low-resource adult patients.This reaction occurs due to a critical decrease in adrenal hormones responsible for adaptation to stress, as a result of which a cascade of vegetative reactions develops (increased heartbeat up to tachycardia, fainting and affective-respiratory crises, pallor or, conversely, redness of the skin with severe sweating, increased breathing, tearfulness), the severity of which can reach the level of somatic disorders, and thereforerequire a differential diagnosis.

Biochemically, such children have frequent sleep disturbances with difficulty falling asleep in their own bed and the need to sleep together with their parents, with typical early morning awakenings, often accompanied by screams and tears, low mood and irritability in the morning.

Due to the lack of hormonal control over the function of the immune system, these children have an increased risk of chronic inflammatory processes and the development of autoimmune diseases, the highest risks of which occur between the ages of 12 and 24 months.In modern children, even minor stress (short-term separation from parents, starting kindergarten, the birth of the youngest child in the family, dental treatment under anesthesia, hospitalization and planned surgery) can cause regression of previously acquired skills and the manifestation of a severe autoimmune disease, such as autism or type 1 diabetes.

As practice has shown, it is the very fact of hospitalization and stress from a sudden change of environment that is traumatic, and not the pain syndrome from manipulations, since they are most often performed under anesthesia.

A child with adrenal dysfunction in a state of depleted hormonal status most often has a number of typical external manifestations: low height and weight, connective tissue dysplasia, dry skin, sparse hair, dry mucous membranes.

The first manifestation that allows us to suspect a violation of hormonal function is sleep disturbance in infants, which develops in the absence of somatic causes (colic, fever, etc.).The baby sleeps only on the chest, needs constant rocking, sleeps extremely lightly and for a short time, waking up immediately when the mother tries to move away from him.

Such children are extremely vulnerable and dependent on their parents; in preschool age they constantly need their presence and tactile contact.These children have a high demand for hugs, kisses, and strokes, which is why they are called “tactile,” “manual,” “sensory,” which often causes affection among parents and specialists until a certain age.One of the extreme manifestations of hormonal deficiency in pre-pubescent children is masturbation, which, unlike in adolescence and adulthood, is devoid of true sexual overtones and is aimed at stimulating the production of hormones by the adrenal glands.Other parasexual reactions to stress include pinching and twisting of the nipples, which was common in both boys and girls we saw at our doctor's appointment.This stimulation has a clear biological and biochemical meaning, since mechanical action on the nipples stimulates the synthesis and release of oxytocin into the bloodstream, which, in turn, has an anti-stress effect.

Depending on the severity of symptoms and laboratory test results, four degrees of adrenal dysfunction are distinguished.To correct mild disorders, you can use vitamin, amino acid and microelement support, and naturopathic adaptogens.In subsequent stages, it is necessary to administer prehormones and boosters, and in case of severe cases, complex hormone replacement therapy.

Unfortunately, in our practice we are increasingly encountering such severe cases of adrenal dysfunction that even low doses of hormonal drugs can produce paradoxical effects.Such phenomena are extremely rare, but recently the number of malnourished children and, as a consequence, the number of behavioral disorders of varying severity has been increasing.

The reason for the increase in the number of patients with adrenal cortex dysfunction among children is the gross increase in the same dysfunction in adults.

In adult patients, adrenal cortex dysfunction also has psychoemotional and somatic manifestations.Psycho-emotional states in PACD (acquired adrenal dysfunction) include anxiety-depressive states, asthenic syndrome, fatigue, decreased performance, memory, motivation, increased irritability, sleep disorders, phobic and obsessive-compulsive disorders, panic attacks.Often, the combination of these symptoms forces the patient to seek help from psychologists, psychotherapists and psychiatrists, which leads to the often unfounded and ineffective prescription of psychotropic medications.When the symptoms of vegetative-vascular dystonia dominate, such patients turn to neurologists with complaints of dizziness, headaches, migraines, intolerance to loud sounds and bright light, fainting and fatigue.Often a clear manifestation of adrenal exhaustion is a noticeable flinch, close to a twitch, in response to an unexpected touch or sound.A patient in this condition prefers to be in a quiet environment with dim lighting, avoiding unnecessary contact with others.Adrenal hormones are involved in the regulation of the menstrual cycle.In patients with PDKN, in addition to dysmenorrhea, there is severe premenstrual syndrome, breast tenderness, swelling, abdominal and back pain, and pronounced changes in the psycho-emotional state.

Due to the fact that adrenal steroid hormones are the most powerful regulators of collagen formation, disruption of the adrenal glands inevitably leads to disruption of collagen synthesis and the prevalence of collagen breakdown processes.Accumulating damage in the structure of connective tissue causes an aseptic inflammatory process of an autoimmune nature with the further development of chronic inflammatory and, as a consequence, pain syndrome.The listed phenomena are combined into the concept of “fibromyalgia”.Chronic debilitating pain in muscles and tendons leads patients to long-term use of anti-inflammatory drugs, most often non-steroidal ones, but they bring only temporary relief of symptoms, since the primary hormonal deficiency persists.

Polyglandular failure

As mentioned above, everything in the body is interconnected.The biosynthesis of hormones is complex in certain chains that are regulated according to the feedback principle.Many hormone functions overlap.Such physiological mechanisms of the organization of the endocrine system allow the body to exist for a long time in a state of relative compensation.If we detect signs of hormonal dysfunction, then, as a rule, this is evidence of the compensatory capabilities of the endocrine system, which means that there is a decrease in the activity or amount of hormones in almost all parts of the endocrine chain.

This condition is called polyglandular insufficiency (PF).There are physiological and pathological types of this dysfunction.

Physiological polyglandular insufficiency includes age-related degeneration of the endocrine system with a uniform decrease in the functional activity of all endocrine glands.Physiological polyglandular insufficiency largely determines the processes associated with aging, that is, a decrease in functional activity, physical strength, endurance, and age-related decline in cognitive functions.

Understanding these mechanisms has made it possible to actively use hormone replacement therapy in anti-aging preventive and treatment programs.

Pathological polyglandular insufficiency can occur at any age and affect any combination of endocrine glands.The mechanisms of development of pathological PN and the “entry points” differ.For example, dysfunction at the level of the thyroid-adrenal axis can begin with adrenal crises and exhaustion due to stress, which will require increased metabolic stress in general and regulation by thyroid hormones, which at this moment are forced to take over the functionality of adrenal hormones.However, such overstrain cannot last long, and the functionality of the thyroid gland is quickly depleted, which is why parallel dysfunction of two hormonal regulation systems develops.

Similar chains of development of dysfunction arise not only in the “adrenal glands – thyroid gland” axis, but also in the “adrenal glands – gonads” axis, as well as in the central neurohumoral axis “hypothalamus – pituitary gland – adrenal glands”, thus closing all endocrine glands into a single system.

Another mechanism for the development of polyglandular insufficiency is autoimmune damage to the endocrine glands.In this case, dysfunction of several organs develops almost at the same time at the same rate, depending on the activity of the systemic inflammatory process, and decompensation of the gland - on the rate of degeneration of its cells and the ability to regenerate.

Thus, the thyroid gland, damaged in the process of autoimmune thyroiditis, can perform its functions of producing hormones for quite a long time even with a high titer of autoantibodies, but the beta cells of the pancreas die much faster, and the regenerative potential is short-term and extremely limited, which determines the need for a quick and accurate selection of a therapeutic strategy for type 1 diabetes mellitus.

In the context of understanding the mechanisms of autoimmune diseases, the presence of an inflammatory autoimmune process of any localization, such as bronchial asthma, Crohn's disease or arthritis, is likely to lead to dysfunction of one or more endocrine glands, usually the thyroid and adrenal glands, within a limited period of time.

Again, if the inflammatory process affects one gland of the axis, then the other glands will also be dysfunctional through the mechanism of exhaustion.Unfortunately, modern medical standards focus attention only on the process that predominates in the clinical picture and only through replacement therapy without affecting the inflammatory link of pathogenesis and supporting glands that are in a state of functional overstrain.

A systematic approach to correcting polyglandular insufficiency, taking into account all the mechanisms of its development, is the only correct strategy for restoring and maintaining a functional resource.

Polyglandular insufficiency is a trigger for the development of a cascade of degenerative processes, as it provokes the development of metabolic syndrome, cardiovascular pathology, and disorders of the central and peripheral nervous systems.Of course, the age, sequence and speed of involvement of organ systems have individual characteristics, as well as the degree of decompensation of each of these systems separately.However, the general direction of the process remains the same.

Polyglandular insufficiency and hormonal dysfunction are the main risk factors for the development of dysregulation of metabolic processes, including at the mitochondrial level.This makes polyglandular deficiency a fundamental factor in the development of mitochondrial dysfunction, and endocrinological intervention an integral part of the therapeutic strategy in mitochondrial medicine.