ADH. What is vasopressin, why is it needed, what is it responsible for

Today he will talk about the more famous hormones - cortisol, oxytocin, melatonin. We encounter their effects every day, but as always, many of them do not work exactly as we expected.

Cortisol

This is a steroid hormone that is released in the adrenal cortex under the influence of adrenocorticotropic hormone (ACTH). Like all steroids, cortisol has the ability to influence the expression of other genes - and this quality of it largely determines its importance.

Cortisol is synthesized as a result of the body's response to stress, and the hormone's task is to accumulate the body's forces and direct them to solve the problem. Cortisol has a “little brother” - adrenaline, which is also secreted in the adrenal medulla. Adrenaline provides an immediate response to stress - blood pressure rises, heart rate increases, and pupils dilate. All this is needed to carry out a quick “fight or flight” reaction. Cortisol acts more slowly and over longer distances.

Under the influence of cortisol, blood sugar levels increase, the immune system is suppressed (so as not to waste energy), and gastric juice is released. Elevated cortisol over time slows wound healing and can stimulate inflammation in the body. Cortisol also reduces the activity of bone tissue building and collagen synthesis.

Under the influence of sunlight on the pituitary gland, cortisol levels begin to rise shortly before waking up and help a person wake up full of energy. During the day, cortisol helps us cope with normal stress (called eustress). This includes any tasks that require our reaction: answering a letter, holding a meeting, preparing statistics. Eustress does not harm our health - on the contrary, it is a necessary level of stress.

But when the level of stress begins to go off scale, eustress turns into distress - stress in its everyday understanding. Initially, these were life-threatening situations, but now they have been supplemented by any events to which a person attaches great importance. This could be overload at work, problems in relationships, failures, worries and losses, as well as a wedding, moving, receiving a Nobel Prize or just a million dollars - stress is not necessarily bad events, but any changes in circumstances that require changes from us. Evolutionarily, a person is prepared to react to stress, but not to be in it constantly. If a stressful situation stretches over time, a permanently elevated level of cortisol begins to negatively affect the body.

First of all, the hippocampus suffers, synaptic connections are destroyed, the volume of the brain decreases: these processes impair thinking and creative abilities. Under the influence of cortisol, especially at an early age, methylation occurs—some genes may be “turned off.” Children who were exposed to severe stress or poor maternal care as children experience changes in their ability to learn—and these changes last a lifetime. In this case, memory will be better able to retain negative impressions, so such children learn better under stress, while ordinary children need a safe environment.

Also, the prolonged effect of cortisol leads to weakened immunity and activation of inflammatory processes. That is why, after a nervous meeting or a sleepless night, a “cold” may appear on the lips - a manifestation of the herpes virus, which, according to statistics, is carried by approximately 67% of the population, but which does not show itself in “peacetime”. Chronic stress leads to early signs of aging - due to the fact that cortisol blocks collagen synthesis, thinning and dehydrating the skin.

Warm hugs, sex, favorite music, meditation, jokes and laughter will help reduce cortisol levels. It helps to get a good night's sleep - and it's not so much the quantity of sleep that matters, but its quality. If you offended someone or had a fight with loved ones, reconciliation will reduce cortisol levels to background levels.

Prolactin

It is a peptide hormone known to be essential for lactation. The pituitary gland is mainly responsible for its synthesis, but in addition to the brain, prolactin is also synthesized by the placenta, mammary glands and even the immune system. Prolactin levels increase many times during pregnancy, childbirth and, most importantly, during breastfeeding. Putting the baby to the breast and biting the nipple stimulates the production of colostrum (a natural protein shake with a high content of immunoglobulins that is secreted by the mammary glands in the first few days after birth) and the transformation of colostrum into milk. Despite the high level of prolactin during pregnancy, lactation begins only after childbirth, when the level of progesterone, which previously prevented the start of the “dairy plant,” drops. Also, high levels of prolactin block the synthesis of follicle-stimulating hormone, which is necessary for ovulation. So regular feedings become a natural hormonal “contraceptive”.

But the effect of prolactin does not end with lactation: it is also a stress hormone. Its level increases in response to anxiety, severe pain, and physical activity. Prolactin has an analgesic effect in inflammatory diseases and, unlike cortisol, activates the immune system - stimulates stem cells to form hematopoiesis and participates in the development of blood vessels.

Prolactin levels increase during crying and orgasm. High levels of prolactin block dopamine D2 receptors, and dopamine, in turn, blocks the secretion of prolactin: from an evolutionary point of view, nursing mothers do not need insatiable curiosity and a desire to learn new things.

Oxytocin

This is an oligopeptide hormone - it consists of several amino acids. It is synthesized by the hypothalamus region of the brain, then it is secreted in the pituitary gland.

In women, oxytocin is released during childbirth - it promotes contractions of the uterus during the first and second stages of contractions. A synthetic version of the hormone is even used to induce labor. Oxytocin reduces sensitivity to pain. In the postpartum period, under the influence of the hormone, bleeding stops and ruptures heal. The level of oxytocin increases many times during lactation - here the hormone acts together with prolactin. The activity of oxytocin receptors is also regulated by estrogen receptors.

In both women and men, oxytocin plays an important role in sexual arousal. The level of oxytocin is increased by hugs (any kind - not necessarily with sexual overtones), sex and orgasm. Oxytocin is considered the bonding hormone - it creates a feeling of trust and calm around a partner. Although, to the same extent, oxytocin can be called the hormone of carelessness: it reduces the perception of alarm and fear signals (but does not in any way affect the causes of such signals).

Oxytocin is a well-known stress fighter: it blocks the release of adrenocorticotropic hormone (ACTH) and, as a result, cortisol (it is ACTH that gives the signal to produce cortisol). Therefore, under the influence of oxytocin, a person feels safe and opens up to the world. The functioning of oxytocin receptors determines how much each of us is able to experience empathy. People with a less active variant of the OXTR gene will have a more difficult time understanding the feelings of others and sharing experiences. According to research, this mechanism plays a role in the development of autism.

With the participation of oxytocin, a rather ancient mechanism for the formation of social bonds in animals is carried out - this is associated with the upbringing of offspring and the need to protect the mother during this period. The main role of oxytocin is in the formation of a mutual bond between mother and child and between partners. Based on his relationship with his mother or any other person who cares for him, the child develops ideas about himself and his personality. The knowledge and experience gained help predict the consequences of actions and form a picture of the world. Oxytocin is also involved in learning.

Vasopressin

Vasopressin is another peptide hormone of the hypothalamus. Vasopressin is also called antidiuretic hormone - it regulates water balance in the body: it reduces the reabsorption of water by the kidneys and retains fluid in the body. Vasopressin contracts vascular smooth muscle and may increase blood pressure. A decrease in the secretion of vasopressin can cause diabetes insipidus, a disease in which the patient produces a huge amount of fluid (more than 6 liters per day) and constant thirst.

Vasopressin plays the role of a neuropeptide and acts on brain cells. It influences social behavior. Thus, a variant of the vasopressin receptor gene AVPR1A is associated with the likelihood of happy family relationships in men - this conclusion was made by comparing genotyping data and survey results. Experiments were conducted on mice that showed that stimulation of vasopressin receptors makes males more attached to their females - they preferred to spend more time with a familiar partner, even if they had previously been polygamous. Here it should be noted that in animals, social monogamy has nothing to do with sexual monogamy - we are talking about attachment to a partner, and not about the complete absence of “extramarital” relationships. In humans, the action of vasopressin as a neuropeptide is not so straightforward.

Oxytocin and vasopressin are paralogues: substances that were created by doubling the DNA sequence and are very similar to each other. Vasopressin begins to be synthesized in the fetus from the 11th week of pregnancy, oxytocin - from the 14th week, and both continue to participate in the development of the infant in the postnatal period. High levels of vasopressin receptor expression during the neonatal period may lead to increased aggression in adults.

While oxytocin levels can vary greatly depending on the situation, vasopressin is a hormone with a smaller range of changes, the level of which is mainly influenced by genetics. The formation of social behavior and stable (or not so stable) connections between partners depends on the activity of vasopressin receptors and their genetic variant. These receptors are also involved in the development of long-term memory and influence the plasticity of cortical neurons.

Melatonin

Let's end today's story on a happy note - let's go to bed. Melatonin, a sleep hormone, is produced by the pineal gland in the brain when it gets dark (which is why shining a smartphone screen into your eyes before bed is a bad idea). It regulates the “internal clock” - circadian rhythms - and helps all body systems go into rest mode. During the day, the highest levels of melatonin occur between midnight and 5 a.m. during daylight hours; throughout the year, melatonin levels increase in winter.

In the body, melatonin is preceded by the amino acid tryptophan, which also plays the role of a precursor to serotonin. Melatonin slows down aging and reproductive functions and increases serotonin levels. The interaction of melatonin with the immune system plays a special role - the hormone’s action reduces inflammation. Melatonin has an antioxidant effect and protects DNA from damage.

Thanks to melatonin, the daily routine is restored after a change in time zone or night work. Decreased melatonin production—for example, due to bright light or changes in daily routine—can cause insomnia, which increases the risk of depression. To help your body get a good night's sleep and regain its routine, try sleeping in the dark—with the lights off and the curtains drawn if you have to sleep during the day.

Life in a big city sometimes consists entirely of stress, chronic lack of sleep, traffic jams, delays, meaningless work meetings and tasks of exaggerated importance and urgency. In such a rhythm, it is very difficult to find time to recover, so we simply begin to take the state of chronic fatigue for granted. But nature did not prepare us for this, and the same cortisol will not be released forever: if you are constantly under stress, cortisol is depleted over time - and then the body is forced to respond to stress in other ways.

To make sure your health is up to par with your stress load, get some advice: Your body may need some support. And I definitely need rest.

Antidiuretic hormone (ADH) is a hormone of the hypothalamus.

Functions of vasopressin

– increases the reabsorption of water by the kidney, therefore increasing the concentration of urine and reducing its volume. It is the only physiological regulator of water excretion by the kidney.

– a number of effects on blood vessels and the brain.

– along with corticotropin-releasing hormone, stimulates the secretion of ACTH.

The final effect of vasopressin on the kidneys is an increase in body water content, an increase in circulating blood volume and dilution of blood plasma.

– increases the tone of the smooth muscles of internal organs, especially the gastrointestinal tract, vascular tone, and causes an increase in peripheral resistance. Due to this, it increases blood pressure. However, its vasomotor effect is small.

– has a hemostatic effect due to spasm of small blood vessels and increased secretion of certain blood clotting factors from the liver. The development of hypertension is facilitated by an increase in the sensitivity of the vascular wall to the constrictor effect observed under the influence of ADH. catecholamines. In this regard, ADH received the name.

– In the brain, it is involved in the regulation of aggressive behavior. It is assumed to be involved in memory mechanisms

– Arginine-vasopressin plays a role in social behavior: in finding a partner, paternal instinct in animals and paternal love in men.

Connection with oxytocin

Vasopressin is chemically very similar to oxytocin, so it can bind to oxytocin receptors and through them has an effect that stimulates tone and contractions of the uterus. The effects of vasopressin are much weaker than those of oxytocin. Oxytocin, binding to vasopressin receptors, has a weak vasopressin-like effect.

The level of vasopressin in the blood increases during shock, trauma, blood loss, pain syndromes, psychosis, and when taking certain medications.

Diseases associated with impaired vasopressin functions.

Diabetes insipidus

In diabetes insipidus, the reabsorption of water in the collecting ducts of the kidneys decreases.

Syndrome of inappropriate antidiuretic hormone secretion

The syndrome is accompanied by increased urine output and problems with the blood. Clinical symptoms are lethargy, anorexia, nausea, vomiting, muscle twitching, convulsions, coma. The patient's condition worsens when large volumes of water enter the body, remission occurs when water consumption is limited.

Vasopressin and social relationships

In 1999, using the example of voles, the following property of vasopressin was discovered. Steppe voles belong to 3% mammals with monogamous relationships. When prairie voles mate, oxytocin and . If the release of these hormones is blocked, sexual relations between prairie voles become as fleeting as those of their “dissolute” mountain relatives. It is blocking that brings the greatest effect.

Rats and mice recognize each other by smell. Scientists suggest that in other monogamous animals and humans, the evolution of the reward mechanism involved in the formation of attachment proceeded in a similar way, including for the purpose of regulating monogamy.

Among the great apes studied, vasopressin levels in the reward centers of the brain monogamous monkeys was higher than that of non-monogamous rhesus monkeys. The more receptors there are in areas associated with reward, the more pleasure the social interaction brings.

An alternative hypothesis is that voles' monogamy is caused by changes in structure and abundance. dopamine receptors .

Vasopressins they are formed only in mammals.

Arginine-vasopressin is formed in representatives of most classes of mammals, and lysine vasopressin- only in some artiodactyls - domestic pigs, wild boars, American pigs, warthogs and hippopotamuses.

The system for regulating social behavior and social relations is associated with neuropeptides - oxytocin And .

These neuropeptides may work and how neurotransmitters(transmit a signal from one neuron to another individually), and how neurohormones(excite many neurons at once, including those located far from the point of neuropeptide release).

Oxytocin and vasopressin- short peptides consisting of nine amino acids, and they differ from each other by only two amino acids.

In all animals studied, these peptides regulate social and sexual behavior, but the specific mechanisms of their action may vary greatly between species.

In snails homologue of vasopressin and oxytocin regulates oviposition and ejaculation. In vertebrates, the original gene was duplicated, and the two resulting neuropeptides diverged: oxytocin affects females more than males.

Oxytocin regulates the sexual behavior of females, childbirth, lactation, attachment to children and marriage partners.

Vasopressin affects erection and ejaculation in a variety of species, including rats, humans, and rabbits, as well as aggression, territorial behavior, and relationships with wives.

If a virgin rat is injected into the brain, it begins to care about other people's rat pups, although in its normal state it is deeply indifferent to them. On the contrary, if a mother rat suppresses the production oxytocin or block oxytocin receptors, she loses interest in her children.

If in rats oxytocin causes concern for children in general, including strangers, then in sheep and people the situation is more complicated: the neuropeptide ensures selective attachment of the mother to her own children.

In voles, which are characterized by strict monogamy, females become attached to their chosen one for life under the influence of oxytocin. Most likely, in this case, the previously existing oxytocin system formation of attachment to children was “co-opted” to form unbreakable marital bonds. In males of the same species, marital fidelity is regulated, as well as .

The formation of personal attachments appears to be one aspect of a more general function oxytocin- regulation of relationships with relatives. For example, mice with the oxytocin gene disabled stop recognizing conspecifics they previously met. Their memory and all senses work normally.

Introduction vasotocin(avian homologue of vasopressin) to male territorial birds makes them more aggressive and makes them sing more, but if the same neuropeptide is administered to male zebra finch, which live in colonies and do not protect their areas, then this does not happen. Apparently, neuropeptides do not create a type of behavior out of nothing, but only regulate existing behavioral stereotypes and predispositions.

It is much more difficult to study everything in humans - who would allow experiments to be carried out with people. However, much can be understood without gross intervention in the genome or brain.

When men are given vasopressin in their noses, other people's faces appear less friendly to them. In women, the effect is the opposite: other people’s faces become more pleasant, and the subjects themselves’ facial expressions become more friendly (in men, on the contrary).

Experiments with administration have so far been carried out only on men (it is more dangerous to do this with women, since oxytocin has a strong effect on female reproductive function). It turned out that oxytocin improves the ability of men to understand the mood of other people by their facial expressions. In addition, men begin to look their interlocutor in the eyes more often.

In other experiments, an effect was found to increase gullibility. Men injected with oxytocin appear to be more generous in the “game of trust.”

According to researchers, society may soon face a whole series of new “bioethical” problems. Should traders be allowed to spray in the air around their goods? oxytocin? Is it possible to prescribe oxytocin drops to quarreling spouses who want to save the family?

The hormone vasopressin binds one person to another, and this is a useful quality. Let there be more of it.)))))))

The hormones vasopressin and oxytocin are synthesized by the ribosomal pathway, and simultaneously 3 proteins are synthesized in the hypothalamus: neurophysin I, II and III, the function of which is to non-covalently bind oxytocin and vasopressin and transport these hormones to the neurosecretory granules of the hypothalamus. Then, in the form of neurophysin–hormone complexes, they migrate along the axon and reach the posterior lobe of the pituitary gland, where they are stored as reserves; After dissociation of the complex, the free hormone is secreted into the blood. Neurophysins were also isolated in pure form, and the primary structure of two of them was elucidated (92 of 97 amino acid residues, respectively); These are cysteine-rich proteins containing seven disulfide bonds.

The chemical structure of both hormones was deciphered by the classical works of V. du Vigneault and co-workers, who first isolated these hormones from the posterior lobe of the pituitary gland and carried out their chemical synthesis. Both hormones are nonapeptides with the following structure:

Vasopressin differs from oxytocin in two amino acids: it contains at position 3 of N-terminal phenylalanine instead of isoleucine and at position 8 - arginine instead of leucine. The indicated sequence of 9 amino acids is characteristic of human, monkey, horse, cattle, sheep and dog vasopressin. The vasopressin molecule from the pig pituitary gland contains lysine instead of arginine at position 8, hence the name “lysine-vasopressin”. In all vertebrates, with the exception of mammals, vasotocin has also been identified. This hormone, consisting of a ring with an S-S bridge of oxytocin and a side chain of vasopressin, was chemically synthesized by V. du Vigneault long before the isolation of the natural hormone. It has been suggested that all neurohypophyseal hormones evolved from one common precursor, namely arginine-vasotocin, from which modified hormones were formed through single mutations of gene triplets.

The main biological effect of oxytocin in mammals is associated with stimulation of contraction of the smooth muscles of the uterus during childbirth and muscle fibers around the alveoli of the mammary glands, which causes milk secretion. Vasopressin stimulates the contraction of smooth muscle fibers of blood vessels, exerting a strong vasopressor effect, but its main role in the body is the regulation of water metabolism, hence its second name, antidiuretic hormone. In small concentrations (0.2 ng per 1 kg of body weight), vasopressin has a powerful antidiuretic effect - it stimulates the reverse flow of water through the membranes of the renal tubules. Normally, it controls the osmotic pressure of blood plasma and the water balance of the human body. With pathology, in particular atrophy of the posterior lobe of the pituitary gland, diabetes insipidus develops - a disease characterized by the release of extremely large amounts of fluid in the urine. In this case, the reverse process of water absorption in the kidney tubules is disrupted.

Regarding the mechanism of action of neurohypophyseal hormones, it is known that hormonal effects, in particular vasopressin, are realized

Melanocyte-stimulating hormones (MSH, melanotropins)

Melanotropins are synthesized and secreted into the blood by the intermediate lobe of the pituitary gland. The primary structures of two types of hormones - α- and β-melanocyte-stimulating hormones (α-MSH and β-MSH) - have been isolated and deciphered. It turned out that in all examined animals α-MSH consists of 13 amino acid residues located in the same sequence:

CH 3 -CO-NH-Ser–Tyr–Ser–Met–Glu–Gis–Phen–Arg–Trp–Gly–Lys–

–Pro–Val-CO-NH 2

In α-MSH, the N-terminal serine is acetylated and the C-terminal amino acid is valinamide.

The composition and structure of β-MSH turned out to be more complex. In most animals, the β-MSH molecule consists of 18 amino acid residues; in addition, there are species differences regarding the nature of the amino acid in positions 2, 6 and 16 of the polypeptide chain of the hormone. β-MSH, isolated from the intermediate lobe of the human pituitary gland, turned out to be a 22-membered peptide extended by 4 amino acid residues from the N-terminus:

N-Ala–Glu–Lys–Lys–Asp–Glu–Gly–Pro–Tyr–Arg–Met–Glu–Gis–Phen– –Arg–Trp–Gly–Ser–Pro–Pro–Lys–Asp-OH

The physiological role of melanotropins is to stimulate melaninogenesis in mammals and increase the number of pigment cells (melanocytes) in the skin of amphibians. It is also possible that MSH influences fur color and the secretory function of sebaceous glands in animals.

Adrenocorticotropic hormone (ACTH, corticotropin)

Back in 1926, it was found that the pituitary gland has a stimulating effect on the adrenal glands, increasing the secretion of cortical hormones. The data accumulated to date indicate that ACTH, produced by basophilic cells of the adenohypophysis, is endowed with this property. ACTH, in addition to its main effect - stimulating the synthesis and secretion of adrenal hormones, has fat-mobilizing and melanocyte-stimulating activity.

The ACTH molecule in all animal species contains 39 amino acid residues. The primary structure of pig and sheep ACTH was deciphered back in 1954–1955. Here is the refined structure of human ACTH:

N-Ser–Tyr–Ser–Met–Glu–Gis–Phen–Arg–Trp–Gly–Lys–Pro–Val–Gly–

–Liz–Liz–Arg–Arg–Pro–Val–Liz–Val–Tyr–Pro–Asp–Ala–Gli–Glu–

–Asp-Gln-Ser-Ala-Glu-Ala-Fen-Pro-Lei-Glu-Fen-ON

Differences in the structure of ACTH from sheep, pigs and bovines concern only the nature of the 31st and 33rd amino acid residues, but all of them are endowed with almost the same biological activity, like ACTH from the human pituitary gland. In the molecule of ACTH, like other protein hormones, although active centers similar to the active centers of enzymes have not been discovered, it is assumed that there are two active sections of the peptide chain, one of which is responsible for binding to the corresponding receptor, the other for the hormonal effect.

Data on the mechanism of action of ACTH on the synthesis of steroid hormones indicate a significant role of the adenylate cyclase system. It is believed that ACTH interacts with specific receptors on the outer surface of the cell membrane (the receptors are represented by proteins in complex with other molecules, in particular with sialic acid). The signal is then transmitted to the enzyme adenylate cyclase, located on the inner surface of the cell membrane, which catalyzes the breakdown of ATP and the formation of cAMP. The latter activates protein kinase, which in turn, with the participation of ATP, phosphorylates cholinesterase, which converts cholesterol esters into free cholesterol, which enters the adrenal mitochondria, which contains all the enzymes that catalyze the conversion of cholesterol into corticosteroids.

Somatotropic hormone (GH, growth hormone, somatotropin)

Growth hormone was discovered in extracts of the anterior pituitary gland back in 1921, but it was obtained in chemically pure form only in 1956–1957. GH is synthesized in acidophilic cells of the anterior pituitary gland; its concentration in the pituitary gland is 5–15 mg per 1 g of tissue, which is 1000 times higher than the concentration of other pituitary hormones. To date, the primary structure of the protein molecule of human, bovine and sheep growth hormone has been fully elucidated. Human GH consists of 191 amino acids and contains two disulfide bonds; The N- and C-terminal amino acids are represented by phenylalanine.

HGH has a wide range of biological effects. It affects all cells of the body, determining the intensity of metabolism of carbohydrates, proteins, lipids and minerals. It enhances the biosynthesis of protein, DNA, RNA and glycogen and at the same time promotes the mobilization of fats from storage and the breakdown of higher fatty acids and glucose in tissues. In addition to activating assimilation processes, accompanied by an increase in body size and skeletal growth, growth hormone coordinates and regulates the rate of metabolic processes. In addition, human and primate (but not other animals) GH has measurable lactogenic activity. It is believed that many of the biological effects of this hormone are carried out through a special protein factor formed in the liver under the influence of the hormone. This factor was called sulfonating or thymidyl because it stimulates the incorporation of sulfate into cartilage, thymidine into vDNA, uridine into RNA, and proline into collagen. By its nature, this factor turned out to be a peptide with a mol. weighing 8000. Considering its biological role, it was given the name “somatomedin”, i.e. mediator actions of growth hormone in the body.

HGH regulates the processes of growth and development of the entire organism, which is confirmed by clinical observations. Thus, with pituitary dwarfism (a pathology known in the literature as panhypopituitarism; associated with congenital underdevelopment of the pituitary gland), there is a proportional underdevelopment of the entire body, including the skeleton, although significant deviations in the development of mental activity are not observed. An adult also develops a number of disorders associated with hypo- or hyperfunction of the pituitary gland. The disease acromegaly is known (from the Greek akros - limb, megas - large), characterized by disproportionately intense growth of individual parts of the body, such as arms, legs, chin, brow ridges, nose, tongue, and the proliferation of internal organs. The disease is apparently caused by a tumor lesion of the anterior pituitary gland.

Lactotropic hormone (prolactin, luteotropic hormone)

Prolactin is considered one of the most “ancient” pituitary hormones, since it can be found in the pituitary gland of lower terrestrial animals that do not have mammary glands, and also has a lactogenic effect in mammals. In addition to the main effect (stimulation of the development of the mammary glands of lactation), prolactin has an important biological significance - it stimulates the growth of internal organs, the secretion of the corpus luteum (hence its second name “luteotropic hormone”), has renotropic, erythropoietic and hyperglycemic effects, etc. Excess prolactin , usually formed in the presence of tumors from prolactin-secreting cells, leads to the cessation of menstruation (amenorrhea) and enlargement of the mammary glands in women and to impotence in men.

The structure of prolactin from the pituitary gland of sheep, bull and humans has been deciphered. This is a large protein, represented by one polypeptide chain with three disulfide bonds, consisting of 199 amino acid residues. Species differences in the amino acid sequence essentially concern 2–3 amino acid residues. Previously, the opinion about the secretion of lactotropin in the human pituitary gland was disputed, since it was assumed that its function was supposedly performed by somatotropin. Currently, convincing evidence has been obtained for the existence of human prolactin, although the pituitary gland contains much less of it than growth hormone. In the blood of women, the level of prolactin increases sharply before childbirth: up to 0.2 ng/l versus 0.01 ng/l normally.

Thyroid-stimulating hormone (TSH, thyrotropin)

Unlike the considered peptide hormones of the pituitary gland, which are represented mainly by one polypeptide chain, thyrotropin is a complex glycoprotein and, in addition, contains two α- and β-subunits, which individually do not have biological activity: they say. its weight is about 30,000.

Thyrotropin controls the development and function of the thyroid gland and regulates the biosynthesis and secretion of thyroid hormones into the blood. The primary structure of the α- and β-subunits of bovine, sheep and human thyrotropin has been completely deciphered: the α-subunit, containing 96 amino acid residues, has the same amino acid sequence in all studied TSH and in all luteinizing hormones of the pituitary gland; The β-subunit of human thyrotropin, containing 112 amino acid residues, differs from the similar polypeptide in cattle TSH in amino acid residues and the absence of C-terminal methionine. Therefore, many authors explain the specific biological and immunological properties of the hormone by the presence of the β-subunit of TSH in complex with the α-subunit. It is assumed that the action of thyrotropin is carried out, like the action of other hormones of a protein nature, through binding to specific receptors of plasma membranes and activation of the adenylate cyclase system (see below).

Lipotropic hormones (LTH, lipotropins)

Among the hormones of the anterior pituitary gland, the structure and function of which have been elucidated in the last decade, lipotropins, in particular β- and γ-LTH, should be noted. The primary structure of sheep and pig β-lipotropin has been studied in most detail; its molecules consist of 91 amino acid residues and have significant species-specific differences in the amino acid sequence. The biological properties of β-lipotropin include a fat-mobilizing effect, corticotropic, melanocyte-stimulating and hypocalcemic activity and, in addition, an insulin-like effect, expressed in increasing the rate of glucose utilization in tissues. It is assumed that the lipotropic effect is carried out through the adenylate cyclase–cAMP–protein kinase system, the final stage of which is the phosphorylation of inactive triacylglycerol lipase. This enzyme, once activated, breaks down neutral fats into diacylglycerol and higher fatty acids (see Chapter 11).

The listed biological properties are due not to β-lipotropin, which turns out to be devoid of hormonal activity, but to its breakdown products formed during limited proteolysis. It turned out that biologically active peptides with opiate-like effects are synthesized in brain tissue and in the intermediate lobe of the pituitary gland. Here are the structures of some of them:

The common type of structure for all three compounds is a tetra-peptide sequence at the N-terminus. It has been proven that β-endorphin (31 AMK) is formed by proteolysis from the larger pituitary hormone β-lipotropin (91 AMK); the latter, together with ACTH, is formed from a common precursor - a prohormone, called proopiocortin(is, therefore, a preprohormone), having a molecular weight of 29 kDa and containing 134 amino acid residues. The biosynthesis and release of proopiocortin in the anterior pituitary gland is regulated by corticoliberin in the hypothalamus. In turn, α- and β-melanocyte-stimulating hormones (α- and β-MSH) are formed from ACTH and β-lipotropin through further processing, in particular limited proteolysis. Using the DNA cloning technique, as well as the Sanger method of determining the primary structure of nucleic acids, the nucleotide sequence of the proopiocortin precursor mRNA was discovered in a number of laboratories. These studies can serve as the basis for the targeted production of new biologically active hormonal therapeutic drugs.

Below are peptide hormones formed from β-lipotropin by specific proteolysis.

Considering the exclusive role of β-lipotropin as a precursor of the listed hormones, we present the primary structure of pig β-lipotropin (91 amino acid residues):

N–Glu–Lei–Ala–Gli–Ala–Pro–Pro–Glu–Pro–Ala–Arg–Asp–Pro–Glu– –Ala–Pro–Ala–Glu–Gli–Ala–Ala–Ala–Arg–Ala –Glu–Lei–Glu–Tir– –Gli–Lei–Val–Ala–Glu–Ala–Glu–Ala–Ala–Glu–Liz–Liz–Asp–Glu– –Gli–Pro–Tir–Liz–Met–Glu –His–Phen–Arg–Trp–Gly–Ser–Pro–Pro– –Lys–Asp–Lys–Arg–Tyr–Gly–Gly–Phen–Met–Tre–Ser–Glu–Lys–Ser– –Gln–Tre –Pro–Lei–Val–Tre–Lei–Phen–Lys–Asn–Ala–Ile–Val–Lys– –Asn–Ala–Gis–Lys–Lys–Gly–Gln–OH

The increased interest in these peptides, in particular enkephalins and endorphins, is dictated by their extraordinary ability, like morphine, to relieve pain. This area of ​​research - the search for new natural peptide hormones and (or) their targeted biosynthesis - is interesting and promising for the development of physiology, neurobiology, neurology and the clinic.

HORMONES OF THE PARATHYROID GLANDS (PARATEHORMONES)

Hormones of a protein nature also include parathyroid hormone (parathyroid hormone), more precisely, a group of parathyroid hormones that differ in the sequence of amino acids. They are synthesized by the parathyroid glands. Back in 1909, it was shown that removal of the parathyroid glands causes tetanic convulsions in animals against the background of a sharp drop in the concentration of calcium in the blood plasma; the introduction of salts of calcium prevented the death of animals. However, it was only in 1925 that an active extract was isolated from the parathyroid glands, causing a hormonal effect - increasing calcium levels in the blood. Pure hormone was obtained in 1970 from the parathyroid glands of cattle; At the same time, its primary structure was determined. It was found that parathyroid hormone is synthesized as a precursor (115 amino acid residues) of proparahormone, but the primary gene product turned out to be a preproparahormone containing an additional signal sequence of 25 amino acid residues. The bovine parathyroid hormone molecule contains 84 amino acid residues and consists of one polypeptide chain.

It was found that parathyroid hormone is involved in the regulation of the concentration of calcium cations and phosphoric acid associated with nimanions in the blood. As is known, the concentration of calcium in the blood serum is a chemical constant; its daily fluctuations do not exceed 3–5% (normally 2.2–2.6 mmol/l). Ionized calcium is considered the biologically active form; its concentration ranges from 1.1–1.3 mmol/l. Calcium ions turned out to be essential factors that are not replaceable by other cations for a number of vital physiological processes: muscle contraction, neuromuscular excitation, blood clotting, cell membrane permeability, activity of a number of enzymes, etc. Therefore, any changes in these processes caused by a long-term lack of calcium in food or a violation of its absorption in the intestine lead to increased synthesis of parathyroid hormone, which promotes the leaching of calcium salts (in the form of citrates and phosphates) from bone tissue and, accordingly, to the destruction of mineral and organic components of bones.

Another target organ of parathyroid hormone is the kidney. Parathyroid hormone reduces the reabsorption of phosphate in the distal tubules of the kidney and increases the tubular reabsorption of calcium.

It should be noted that trihormones play a major role in the regulation of Ca 2+ concentration in extracellular fluid: parathyroid hormone, calcitonin, synthesized in the thyroid gland (see below), and calcitriol, a derivative of D 3 (see Chapter 7). All three hormones regulate Ca 2+ levels, but their mechanisms of action are different. Thus, the main role of calcitriol is to stimulate the absorption of Ca 2+ phosphate in the intestine, against a concentration gradient, while parathyroid hormone promotes their release from bone tissue into the blood, the absorption of calcium in the kidneys and the release of phosphates in the urine. The role of calcitonin in the regulation of Ca 2+ homeostasis in the body has been less studied. It should also be noted that the mechanism of action of calcitriol at the cellular level is similar to the action of steroid hormones (see below).

It is considered proven that the physiological effect of parathyroid hormone on kidney and bone tissue cells is realized through the adenylate cyclase-cAMP system (see below).

Liberians:

• Thyroliberin;
• corticoliberin;
• somatoliberin;
• prolactoliberin;
• melanoliberin;
• gonadoliberin (lyuliberin and follyliberin)

• somatostatin;
• prolactostatin (dopamine);
• melanostatin;
• corticostatin

Neuropeptides:

• enkephalins (leucine-enkephalin (leu-enkephalin), methionine-enkephapine (met-enkephalin));
• endorphins (a-endorphin, (β-endorphin, γ-endorphin);
• dynorphins A and B;
• proopiomelanocortin;
• neurotensin;
• substance P;
• kyotorphin;
• vasointestinal peptide (VIP);
• cholecystokinin;
• neuropeptide-Y;
• agouterine protein;
• orexins A and B (hypocretins 1 and 2);
• ghrelin;
• delta sleep inducing peptide (DSIP), etc.

Hypothalamic-posterior pituitary hormones:

• vasopressin or antidiuretic hormone (ADH);
• oxytocin

Monoamines:

• serotonin;
• norepinephrine;
• adrenalin;
• dopamine

Effector hormones of the hypothalamus and neurohypophysis

Effector hormones of the hypothalamus and neurohypophysis are vasopressin and oxytocin. They are synthesized in magnocellular neurons of the SON and PVN of the hypothalamus, delivered by axonal transport to the neurohypophysis and released into the blood of the capillaries of the inferior pituitary artery (Fig. 1).

Vasopressin

Antidiuretic hormone(ADG, or vasopressin) - a peptide consisting of 9 amino acid residues, its content is 0.5 - 5 ng/ml.

Basal secretion of the hormone has a daily rhythm with a maximum in the early morning hours. The hormone is transported in the blood in free form. Its half-life is 5-10 minutes. ADH acts on target cells through stimulation of membrane 7-TMS receptors and second messengers.

Functions of ADH in the body

The target cells of ADH are the epithelial cells of the renal collecting ducts and the smooth myocytes of the vascular walls. Through stimulation of V 2 receptors in the epithelial cells of the collecting ducts of the kidneys and an increase in the level of cAMP in them, ADH increases water reabsorption (by 10-15%, or 15-22 l/day), promotes concentration and reduction in the volume of final urine. This process is called antidiuresis, and the vasopressin that causes it is called ADH.

In high concentrations, the hormone binds to V 1 receptors of vascular smooth myocytes and, through an increase in the level of IPG and Ca 2+ ions in them, causes contraction of myocytes, narrowing of the arteries and an increase in blood pressure. This effect of the hormone on the blood vessels is called pressor, hence the name of the hormone - vasopressin. ADH is also involved in the stimulation of ACTH secretion under stress (through V 3 receptors and intracellular IPG and Ca 2+ ions), the formation of thirst motivation and drinking behavior, and in memory mechanisms.

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

The synthesis and release of ADH under physiological conditions stimulate an increase in osmotic pressure (hyperosmolarity) of the blood. Hyperosmolarity is accompanied by activation of osmosensitive neurons of the hypothalamus, which in turn stimulate the secretion of ADH by neurosecretory cells of the SOY and PVN. These cells are also associated with neurons of the vasomotor center, which receive information about blood flow from the mechano- and baroreceptors of the atria and sinocarotid zone. Through these connections, the secretion of ADH is reflexively stimulated when the circulating blood volume (CBV) decreases and blood pressure drops.

Main effects of vasopressin

• Activates
• Stimulates contraction of vascular smooth muscle
• Activates the thirst center
• Participates in learning mechanisms and
• Regulates thermoregulation processes
• Performs neuroendocrine functions, being a mediator of the autonomic nervous system
• Participates in the organization
• Influences emotional behavior

Increased ADH secretion is also observed with increased blood levels of angiotensin II, stress and physical activity.

The release of ADH decreases with a decrease in blood osmotic pressure, an increase in blood volume and (or) blood pressure, and the effect of ethyl alcohol.

Insufficiency of the secretion and action of ADH may be a consequence of insufficiency of the endocrine function of the hypothalamus and neurohypophysis, as well as dysfunction of ADH receptors (absence, decreased sensitivity of V 2 receptors in the epithelium of the collecting ducts of the kidneys), which is accompanied by excessive excretion of low-density urine up to 10-15 l/day and hypohydration of body tissues. This disease was named diabetes insipidus. Unlike diabetes, in which excess urine production is caused by elevated levels of glucose in the blood, diabetes insipidus Blood glucose levels remain normal.

Excessive secretion of ADH is manifested by a decrease in diuresis and water retention in the body, up to the development of cellular edema and water intoxication.

Oxytocin

Oxytocin- a peptide consisting of 9 amino acid residues, transported by the blood in free form, half-life - 5-10 minutes, acts on target cells (smooth myocytes of the uterus and myoepitslial cells of the mammary gland ducts) through stimulation of membrane 7-TMS receptors and an increase in them the level of IPE and Ca 2+ ions.

Functions of oxytocin in the body

An increase in hormone levels, observed naturally towards the end of pregnancy, causes increased contraction of the uterus during childbirth and the postpartum period. The hormone stimulates the contraction of myoepithelial cells of the mammary gland ducts, promoting milk secretion when feeding newborns.

Main effects of oxytocin:

• Stimulates uterine contractions
• Activates milk secretion
• Has diuretic and natriuretic effects, participating in water-salt behavior
• Regulates drinking behavior
• Increases the secretion of adenohypophysis hormones
• Participates in learning and memory mechanisms
• Has a hypotensive effect

The synthesis of oxytocin increases under the influence of increased levels of estrogen, and its release is enhanced reflexively by irritation of the mechanoreceptors of the cervix during its distension during childbirth, as well as by stimulation of the mechanoreceptors of the nipples of the mammary glands during feeding of the child.

Insufficient function of the hormone is manifested by weakness of labor in the uterus and impaired milk secretion.

Hypothalamic releasing hormones are discussed when presenting the functions of the peripheral endocrine glands.

- Axons extend from the neurosecretory nuclei of the hypothalamus (supraoptic and paraventricular) to the pituitary gland

- These axons carry hormones packed into granules into the posterior lobe of the pituitary gland.

- There is no hormone synthesis in the posterior lobe of the pituitary gland (neurohypophysis).

- The anterior part of the pituitary gland (adenohypophysis) secretes a whole set of peptide hormones. The adenohypophysis is under the control of special chemical factors that are secreted by the neurons of the hypothalamus and released from the axon endings of these cells in the median eminence at the base of the pituitary stalk, from where the blood flow reaches the adenohypophysis cells. Four of these factors are called liberins, and tristatins

- Liberins stimulate the secretion of the corresponding hormones by the cells of the adenohypophysis

- Statins inhibit the secretion of the corresponding hormones

- Liberins and statins are short peptides consisting of a small number

amino acid residues. The membrane type of reception is characteristic.

Corticoliberin is produced in the hypothalamus, stimulates the release of ACTH into the blood

Thyroid-releasing hormone of the hypothalamus (short peptide) consists of 3 amino acid residues, regulates the synthesis and release of thyroid-stimulating hormone, can directly influence brain cells, activating emotional behavior and maintaining wakefulness, increasing breathing, suppressing appetite, mitigating the course of depression

Luliberin - hypothalamic liberin, which controls the regulation of gonadotropins (follicle-stimulating and luteinizing hormones) consists of 10 amino acid residues; It is also able to act on brain cells, activating sexual behavior, increasing emotionality and improving learning and memory.

A decrease in luliberin is found in anorexia nervosa

Somatoliberin stimulates the formation and release of somatotropin

Somatostatin inhibits these processes

It is also worth noting that in the islets of Largehans (pancreas), in delta (15%), somatostatin is produced.

PROLAKTO-STATIN (Prolactin) from dopamine

Melanostatin inhibits the release of melanocyte-stimulating hormone. In addition to the direct effect on the pituitary gland, it activates emotional and motor activity, directly affecting brain functions. Has an antidepressant effect and is used for Parkinsonism

- From the nerve endings of the cells of the hypothalamus, 2 peptide hormones enter the vessels of the posterior lobe of the pituitary gland, each of which consists of 9 amino acid residues: antidiuretic hormone (ADH = vasopressin) and oxytocin

- The target organ for vasopressin is the kidney

- Vasopressin is produced in neurons of the supraoptic nucleus of the hypothalamus, enters the posterior lobe of the pituitary gland along axons, and from there reaches the collecting ducts and excretory ducts of the kidneys through the bloodstream.

- Under the influence of vasopressin, the reabsorption of water from urine increases, which prevents large fluid losses

- In increased concentrations, vasopressin acts on the muscles of the artery walls: they contract, the vessels narrow and blood pressure increases.

- Vasopressin - “vasoconstrictor”

- The release of vasopressin into the blood increases with large blood losses, when the pressure drops and needs to be increased

- Vasopressin also affects the brain and is a natural stimulator of learning and memory.

- In small doses, it can accelerate learning, slow down forgetting, and restore memory after severe injuries.

- With a decrease in vasopressin doses (due to traumatic brain injuries, brain tumors and meningitis), diabetes insipidus develops

- Symptoms of the disease:

1) a sharp increase in urine volume (up to 20 liters per day)

At the same time, there is no excess sugar in the urine as in diabetes mellitus. This is due to the fact that without vasopersin it is impossible to ensure the reabsorption of water from urine into the blood

Now they have learned to produce vasopressin synthetically and use it to treat diabetes insipidus

In severe cases, the target organ is not able to respond even to large concentrations of vasopressin, this is due to the fact that vasopressin receptors located in the collecting ducts and excretory ducts lose sensitivity to the hormone.

Oxytocin (OT) in most cases is produced in neurons of the paraventricular nucleus of the hypothalamus, transported along axons to the neurohypophysis and from there enters the blood

Target tissues of OT: smooth muscle of the uterus and muscle cells surrounding the ducts of the mammary glands and testes

Towards the end of pregnancy (after 280 days), the secretion of oxytocin increases, which leads to contraction of the smooth muscles of the uterus, the fetus moves towards the cervix and vagina, which leads to childbirth. After childbirth, oxytocin secretion is inhibited

If the secretion of oxytocin is insufficient, childbirth is impossible: it is necessary to resort to artificial stimulation by injecting the woman in labor with synthetic oxytocin