Intracellular hormone receptors. Secondary messenger mechanisms

Questions to prepare for the lesson:

1. Hormonal regulation as a mechanism of intercellular and interorgan coordination of metabolism. The main mechanisms of metabolism regulation: changes in the activity of enzymes in the cell, changes in the amount of enzymes in the cell (induction or repression of synthesis), changes in the permeability of cell membranes.

2. Hormones, general characteristics, classification of hormones by chemical structure and biological functions. The mechanism of action of protein hormones.

3. The mechanism of action of steroid hormones and thyroxine.

4. Hormones of the hypothalamus. Luliberin, somatostatin, thyroliberin.

5. Pituitary hormones. Posterior pituitary hormones: vasopressin, oxytocin.

6. Structure of synthesis and metabolism of iodothyronines.

7. The influence of iodothyronines on metabolism. Hypo- and hyperthyroidism.

8. Hormones of the adrenal medulla. Structure, influence on metabolism. Biosynthesis of catecholamines.

9. Growth hormone, structure, functions.

10. Hormones of the parathyroid glands. Regulation of phosphorus-calcium metabolism.

11. Insulin. Glucagon. Effect on metabolism.

12. Hormonal picture of insulin-dependent diabetes mellitus

13. Hormonal picture of non-insulin-dependent diabetes mellitus

14. Steroid hormones. Glucocorticoids.

15. Sex hormones.

16. Renin-angiotensin system.

17. Kallikrein-kinin system.

Complete the tasks:

1. Liberians:

A. Small peptides

B. Interact with cytoplasmic receptors.

B. Activate the secretion of tropic hormones.

D. They transmit a signal to the receptors of the anterior pituitary gland.

D. Cause insulin secretion.

2. Choose the incorrect statement. cAMP:

A. Participates in the mobilization of glycogen.

B. Second signal messenger.

B. Protein kinase activator.

D. Coenzyme adenylate cyclase.

D. Phosphodiesterase substrate.

3. Arrange the events that occur during the synthesis of iodothyronines in the required order, using numerical notation:

A. Iodination of tyrosine residues in thyroglobulin.

B. Thyroglobulin synthesis.

B. Condensation of iodinated tyrosine residues.

D. Transport of iodothyronines into target cells.

D. Formation of a complex with thyroxine-binding protein.

4. Arrange the listed metabolites in the order of their formation:

A. 17-OH-progesterone.

B. Pregnenolone.

B. Cholesterol.

G. Progesterone

D. Cortisol.

5. Select a hormone whose synthesis and secretion increases in response to an increase in osmotic pressure:

A. Aldosterone.

B. Cortisol.

B. Vasopressin.

G. Adrenaline.

D. Glucagon.

6. Under the influence of insulin, the liver accelerates:

A. Protein biosynthesis

B. Biosynthesis of glycogen.

B. Gluconeogenesis.

D. Biosynthesis of fatty acids.

D. Glycolysis.

7. For a three-day fast, all of the following are true, except:

A. The insulin-glucagon index is reduced.

B. The rate of gluconeogenesis from amino acids increases.

B. The rate of TAG synthesis in the liver decreases.

D. The rate of b-oxidation in the liver decreases.

D. The concentration of ketone bodies in the blood is higher than normal.

8. In diabetes mellitus, the following occurs in the liver:

A. Acceleration of glycogen synthesis.

B. Reduced rate of gluconeogenesis from lactate.

B. Reduced rate of glycogen mobilization.

D. Increasing the rate of acetoacetate synthesis.

D. Increased activity of acetyl-CoA carboxylase.

9. With NIDDM, the following are most often found in patients:

A. Hyperglucosemia.

B. Reduced rate of insulin synthesis.

B. The concentration of insulin in the blood is normal or higher than normal.

D. Antibodies to pancreatic b-cells.

D. Microangiopathies.

LAB WORK 14

Topic: Construction and analysis of glycemic curves

Target: Study the intermediate metabolism of carbohydrates, the role of carbohydrates in energy metabolism. Clinical and diagnostic value of the sugar load method for diabetes mellitus, Addison's disease, hypothyroidism, etc.

Principle of the method : The determination of glucose is based on a reaction catalyzed by glucose oxidase:

glucose + O 2 gluconolactone + H 2 O 2

The hydrogen peroxide formed during this reaction causes the oxidation of peroxidase substrates to form a colored product.

Sugar load method: In the morning, on an empty stomach, blood is taken from the patient’s finger and the blood glucose concentration is determined. After this, give 50 - 100 g of glucose in 200 ml of warm boiled water (1 g of glucose per 1 kg of weight) to drink for no more than 5 minutes. Then the blood glucose level is re-examined by taking blood from the finger every 30 minutes for 2-3 hours. A graph is constructed in the coordinates: time - glucose concentration in the blood serum, and the diagnosis is made or clarified by the type of graph.

Progress: Serum samples (before and after glucose ingestion) are tested for glucose concentration. To do this, add 2 ml of the working reagent (phosphate buffer, peroxidase + glucose oxidase substrates in a ratio of 40:1) into a series of test tubes. 0.05 ml of a standard glucose solution with a concentration of 10 mmol/l is added to one of the test tubes. In others - 0.05 ml of blood serum taken using the sugar load method. The solutions are shaken and incubated at room temperature for 20 minutes.

After incubation, the optical density of the solutions is measured using FEC at a wavelength of 490 nm. A cuvette with an optical path length of 5 mm. The reference solution is the working reagent.

Calculation of glucose concentration:

C = 10 mmol/l

where E op is the optical density in serum samples;

E st - optical density of a standard glucose solution

Analysis result:

Schedule:

Conclusion:

Date: Teacher's signature:

PRACTICAL LESSON

Test 3 Hormonal regulation of metabolism

According to this mechanism, which is called calcium-phospholipid mechanism, act vasopressin(via V 1 receptors), adrenalin(via α 1 -adrenergic receptors), angiotensin II.

The principle of operation of this mechanism coincides with the previous one, but instead of adenylate cyclase, the target enzyme for the α-subunit is phospholipase C(FL S). Phospholipase C cleaves membrane phospholipid phosphatidylinositol diphosphate(FIF 2) to secondary messengers inositol triphosphate(IF 3) and diacylglycerol(DAG).

General diagram of the calcium-phospholipid mechanism of hormone action

Signal Transmission Stages

The signal transmission stages are as follows:

1. Interaction hormone With receptor leads to a change in the conformation of the latter.
2. This change is transmitted to G protein(GTP, GTP-dependent) which consists of three subunits (αP, β and γ), the α subunit is associated with GDP.
3. As a result of interaction with the receptor β- And γ- subunits split off, simultaneously on αP - GDP subunit is replaced by GTF.
4. The α P subunit activated in this way stimulates phospholipase C, which begins the splitting of FIF 2 into two secondary messengers - IF 3 And DAG.
5. Inositol triphosphate opens calcium channels in the endoplasmic reticulum, which causes an increase in concentration Ca 2+ ions. Diacylglycerol together with Ca 2+ ions, it activates protein kinase C. In addition, diacylglycerol has another signaling function: it can decompose into 1-monoacylglycerol And polyene fatty acid(usually arachidonic acid), from which eicosanoids are formed.
6. Protein kinase C phosphorylates a number of enzymes and generally participates in the processes of cell proliferation. Accumulation Ca 2+ ions in the cytoplasm causes activation of certain calcium-binding proteins (for example, calmodulin,annexin,Troponin C).
7. Hydrolysis of PIF 2 continues for some time until the α P subunit, which is GTPase, splits phosphate from GTP.
8. As soon as GTP is converted into GDP, the α P subunit inactivated, loses its effect on phospholipase C, binds back to the β- and γ-subunits.
   Everything returns to its original position.
9. Hormone detaches from the receptor even earlier:

• If hormone concentration in blood great, then its next molecule will attach to the receptor after a short period of time and the mechanism will restart quickly - the corresponding processes are activated in the cell.
• If hormone in blood few– there is some pause for the cell, there is no change in metabolism.

The hormone molecule is usually called the primary mediator of the regulatory effect, or ligand. Molecules of most hormones bind to receptors specific to them on the plasma membranes of target cells, forming a ligand-receptor complex. For peptide, protein hormones and catecholamines, its formation is the main initial link in the mechanism of action and leads to the activation of membrane enzymes and the formation of various secondary messengers of the hormonal regulatory effect, which realize their action in the cytoplasm, organelles and cell nucleus. Among the enzymes activated by the ligand-receptor complex are described: adenylate cyclase, guanylate cyclase, phospholipases C, D and A2, tyrosine kinases, phosphate-tyrosine phosphatases, phosphoinositide-3-OH-kinase, serine threonine kinase, NO synthase, etc. Secondary messengers, formed under the influence of these membrane enzymes are: 1) cyclic adenosine monophosphate (cAMP); 2) cyclic guanosine monophosphate (cGMP); 3) inositol-3-phosphate (IPZ); 4) diacylglycerol; 5) oligo (A) (2,5-oligoisoadenylate); 6) Ca2+ (ionized calcium); 7) phosphatidic acid; 8) cyclic adenosine diphosphate ribose; 9) NO (nitric oxide). Many hormones, forming ligand-receptor complexes, cause the simultaneous activation of several membrane enzymes and, accordingly, second messengers.

Mechanisms of action of peptide, protein hormones and catecholamines. Ligand. A significant part of hormones and biologically active substances interact with the family of receptors associated with G-proteins of the plasma membrane (andrenaline, norepinephrine, adenosine, angiotensin, endothelium, etc.).

Basic systems of secondary intermediaries.

Adenylate cyclase system - cAMP. The membrane enzyme adenylate cyclase can be found in two forms - activated and non-activated. Activation of adenylate cyclase occurs under the influence of a hormone-receptor complex, the formation of which leads to the binding of guanyl nucleotide (GTP) to a special regulatory stimulating protein (GS protein), after which the GS protein causes the addition of Mg to adenylate cyclase and its activation. This is how hormones that activate adenylate cyclase act - glucagon, thyrotropin, parathyrin, vasopressin (through V-2 receptors), gonadotropin, etc. A number of hormones, on the contrary, suppress adenylate cyclase - somatostatin, angiotensin-II, etc. The hormone receptor complexes of these hormones interact in cell membrane with another regulatory inhibitory protein (GI protein), which causes hydrolysis of guanosine triphosphate (GTP) to guanosine diphosphate (GDP) and, accordingly, suppression of adenylate cyclase activity. Adrenaline activates adenylate cyclase through β-adrenergic receptors, and suppresses it through alpha1-adrenergic receptors, which largely determines the differences in the effects of stimulation of different types of receptors. Under the influence of adenylate cyclase, cAMP is synthesized from ATP, which causes activation of two types of protein kinases in the cell cytoplasm, leading to phosphorylation of numerous intracellular proteins. This increases or decreases membrane permeability, activity and quantity of enzymes, i.e. causes metabolic and, accordingly, functional changes in cell activity typical for the hormone. In table Table 6.2 shows the main effects of activation of cAMP-dependent protein kinases.

The transmethylase system provides methylation of DNA, all types of RNA, chromatin and membrane proteins, a number of hormones at the tissue level, and membrane phospholipids. This contributes to the implementation of many hormonal influences on the processes of proliferation, differentiation, the state of membrane permeability and the properties of their ion channels and, which is especially important to emphasize, affects the availability of membrane receptor proteins to hormone molecules. The cessation of the hormonal effect realized through the adenylate cyclase - cAMP system is carried out using a special enzyme, cAMP phosphodiesterase, which causes hydrolysis of this secondary messenger with the formation of adenosine-5-monophosphate. However, this hydrolysis product is converted in the cell into adenosine, which also has the effects of a second messenger, since it suppresses methylation processes in the cell.

Guanylate cyclase-cGMP system. Activation of membrane guanylate cyclase occurs not under the direct influence of the hormone-receptor complex, but indirectly through ionized calcium and oxidant membrane systems. The stimulation of guanylate cyclase activity, which determines the effects of acetylcholine, also occurs indirectly through Ca2+. Through activation of guanylate cyclase, the effect of atrial natriuretic hormone, atriopeptide, is realized. By activating peroxide oxidation, the vascular wall endothelial hormone nitric oxide, a relaxing endothelial factor, stimulates guanylate cyclase. Under the influence of guanylate cyclase, cGMP is synthesized from GTP, which activates cGMP-dependent protein kinases, which reduce the rate of phosphorylation of myosin light chains in the smooth muscles of the vascular walls, leading to their relaxation. In most tissues, the biochemical and physiological effects of cAMP and cGMP are opposite. Examples include stimulation of cardiac contractions under the influence of cAMP and inhibition of contractions by cGMP, stimulation of contraction of intestinal smooth muscles by cGMP and inhibition of cAMP. cGMP ensures hyperpolarization of retinal receptors under the influence of light photons. Enzymatic hydrolysis of cGMP, and consequently the cessation of the hormonal effect, is carried out using a specific phosphodiesterase.

Phospholipase C system - inositol-3-phosphate. The hormone receptor complex with the participation of the regulatory G protein leads to the activation of the membrane enzyme phospholipase C, which causes hydrolysis of membrane phospholipids with the formation of two second messengers: inositol-3-phosphate and diacylglycerol. Inositol-3-phosphate causes the release of Ca2+ from intracellular stores, mainly from the endoplasmic reticulum, ionized calcium binds to the specialized protein calmodulin, which ensures the activation of protein kinases and phosphorylation of intracellular structural proteins and enzymes. In turn, diacylglycerol promotes a sharp increase in the affinity of protein kinase C for ionized calcium, the latter activates it without the participation of calmodulin, which also culminates in the processes of protein phosphorylation. Diacylglycerol simultaneously implements another way of mediating the hormonal effect by activating phospholipase A-2. Under the influence of the latter, arachidonic acid is formed from membrane phospholipids, which is a source of substances with powerful metabolic and physiological effects - prostaglandins and leukotrienes. In different cells of the body, one or another pathway for the formation of secondary messengers prevails, which ultimately determines the physiological effect of the hormone. Through the considered system of second messengers, the effects of adrenaline (in connection with the alpha-adrenoreceptor), vasopressin (in connection with the V-1 receptor), angiotensin-I, somatostatin, and oxytocin are realized.

Calcium-calmodulin system. Ionized calcium enters the cell after the formation of the hormone-receptor complex either from the extracellular environment due to the activation of slow membrane calcium channels (as happens, for example, in the myocardium), or from intracellular stores under the influence of inositol-3-phosphate. In the cytoplasm of non-muscle cells, calcium binds to a special protein, calmodulin, and in muscle cells, the role of calmodulin is played by troponin C. Calmodulin bound to calcium changes its spatial organization and activates numerous protein kinases, which ensure phosphorylation, and therefore changes in the structure and properties of proteins. In addition, the calcium-calmodulin complex activates cAMP phosphodiesterase, which suppresses the effect of the cyclic compound as a second messenger. Caused by a hormonal stimulus, a short-term increase in calcium in the cell and its binding to calmodulin is a trigger for numerous physiological processes - muscle contraction, secretion of hormones and release of mediators, DNA synthesis, changes in cell motility, transport of substances through membranes, changes in enzyme activity.

Secondary intermediary relationships Several secondary messengers are present or can be formed simultaneously in the cells of the body. In this regard, various relationships are established between secondary messengers: 1) equal participation, when different messengers are necessary for a full hormonal effect; 2) one of the intermediaries is the main one, and the other only contributes to the implementation of the effects of the first; 3) mediators act sequentially (for example, inositol-3-phosphate ensures the release of calcium, diacylglycerol facilitates the interaction of calcium with protein kinase C); 4) intermediaries duplicate each other to ensure redundancy for the purpose of reliable regulation; 5) mediators are antagonists, i.e. one of them turns on the reaction, and the other inhibits it (for example, in vascular smooth muscles, inositol-3-phosphate and calcium realize their contraction, and cAMP - relaxation).

The systems of secondary messengers of hormone action are:

1. Adenylate cyclase and cyclic AMP,

2. Guanylate cyclase and cyclic GMP,

3. Phospholipase C:

Diacylglycerol (DAG),

Inositol tri-phosphate (IF3),

4. Ionized Ca – calmodulin

Heterotromic protein G protein.

This protein forms loops in the membrane and has 7 segments. They are compared to serpentine ribbons. It has protruding (outer) and inner parts. The hormone is attached to the outer part, and on the inner surface there are 3 subunits - alpha, beta and gamma. In its inactive state, this protein has guanosine diphosphate. But upon activation, guanosine diphosphate changes to guanosine triphosphate. A change in the activity of the G protein leads either to a change in the ionic permeability of the membrane, or to the activation of the enzyme system in the cell (adenylate cyclase, guanylate cyclase, phospholipase C). This causes the formation of specific proteins, protein kinase is activated (necessary for phosphorylation processes).

G proteins can be activating (Gs) and inhibitory, or in other words, inhibitory (Gi).

The destruction of cyclic AMP occurs under the action of the enzyme phosphodiesterase. Cyclic GMF has the opposite effect. When phospholipase C is activated, substances are formed that promote the accumulation of ionized calcium inside the cell. Calcium activates protein cinases and promotes muscle contraction. Diacylglycerol promotes the conversion of membrane phospholipids into arachidonic acid, which is the source of the formation of prostaglandins and leukotrienes.

The hormone receptor complex penetrates the nucleus and acts on DNA, which changes transcription processes and produces mRNA, which leaves the nucleus and goes to the ribosomes.

Therefore, hormones can have:

1. Kinetic or starting action,

2. Metabolic action,

3. Morphogenetic effect (tissue differentiation, growth, metamorphosis),

4. Corrective action (corrective, adapting).

Mechanisms of action of hormones in cells:

Changes in cell membrane permeability,

Activation or inhibition of enzyme systems,

Impact on genetic information.

Regulation is based on the close interaction of the endocrine and nervous systems. Excitation processes in the nervous system can activate or inhibit the activity of the endocrine glands. (Consider, for example, the process of ovulation in a rabbit. Ovulation in a rabbit occurs only after mating, which stimulates the release of gonadotropic hormone from the pituitary gland. The latter causes the ovulation process).

After suffering mental trauma, thyrotoxicosis may occur. The nervous system controls the release of pituitary hormones (neurohormones), and the pituitary gland influences the activity of other glands.

Feedback mechanisms exist. The accumulation of a hormone in the body leads to inhibition of the production of this hormone by the corresponding gland, and the deficiency will be a mechanism for stimulating the formation of the hormone.

There is a mechanism of self-regulation. (For example, the level of glucose in the blood determines the production of insulin and (or) glucagon; if the sugar level increases, insulin is produced, and if it decreases, glucagon is produced. Na deficiency stimulates the production of aldosterone).

5. Hypothalamic-pituitary system. Its functional organization. Neurosecretory cells of the hypothalamus. Characteristics of tropic hormones and releasing hormones (liberins, statins). Epiphysis (pineal gland).

6. Adenohypophysis, its connection with the hypothalamus. The nature of the action of hormones of the anterior pituitary gland. Hypo- and hypersecretion of adenohypophysis hormones. Age-related changes in the formation of hormones in the anterior lobe.

The cells of the adenohypophysis (see their structure and composition in the histology course) produce the following hormones: somatotropin (growth hormone), prolactin, thyrotropin (thyroid-stimulating hormone), follicle-stimulating hormone, luteinizing hormone, corticotropin (ACTH), melanotropin, beta-endorphin, diabetogenic peptide, exophthalmic factor and ovarian growth hormone. Let's take a closer look at the effects of some of them.

Corticotropin . (adrenocorticotropic hormone - ACTH) is secreted by the adenohypophysis in continuously pulsating bursts that have a clear daily rhythm. The secretion of corticotropin is regulated by direct and feedback connections. The direct connection is represented by the hypothalamic peptide - corticoliberin, which enhances the synthesis and secretion of corticotropin. Feedback is triggered by the content of cortisol in the blood (a hormone of the adrenal cortex) and is closed both at the level of the hypothalamus and the adenohypophysis, and an increase in the concentration of cortisol inhibits the secretion of corticotropin and corticotropin.

Corticotropin has two types of action - adrenal and extra-adrenal. The adrenal gland effect is the main one and consists of stimulating the secretion of glucocorticoids, and to a much lesser extent, mineralocorticoids and androgens. The hormone enhances the synthesis of hormones in the adrenal cortex - steroidogenesis and protein synthesis, leading to hypertrophy and hyperplasia of the adrenal cortex. The extra-adrenal effect consists of lipolysis of adipose tissue, increased insulin secretion, hypoglycemia, increased melanin deposition with hyperpigmentation.

Excess corticotropin is accompanied by the development of hypercortisolism with a predominant increase in cortisol secretion and is called “Itsenko-Cushing’s disease.” The main manifestations are typical for excess glucocorticoids: obesity and other metabolic changes, a decrease in the effectiveness of immune mechanisms, the development of arterial hypertension and the possibility of diabetes. Corticotropin deficiency causes insufficiency of glucocorticoid function of the adrenal glands with pronounced metabolic changes, as well as a decrease in the body's resistance to unfavorable environmental conditions.

Somatotropin. . Growth hormone has a wide range of metabolic effects that provide morphogenetic effects. The hormone affects protein metabolism, enhancing anabolic processes. It stimulates the supply of amino acids into cells, protein synthesis by accelerating translation and activating RNA synthesis, increases cell division and tissue growth, and inhibits proteolytic enzymes. Stimulates the incorporation of sulfate into cartilage, thymidine into DNA, proline into collagen, uridine into RNA. The hormone causes a positive nitrogen balance. Stimulates the growth of epiphyseal cartilage and their replacement with bone tissue by activating alkaline phosphatase.

The effect on carbohydrate metabolism is twofold. On the one hand, somatotropin increases insulin production both due to a direct effect on beta cells and due to the hormone-induced hyperglycemia caused by the breakdown of glycogen in the liver and muscles. Somatotropin activates liver insulinase, an enzyme that destroys insulin. On the other hand, somatotropin has a contrainsular effect, inhibiting the utilization of glucose in tissues. This combination of effects, in the presence of a predisposition in conditions of excessive secretion, can cause diabetes mellitus, called pituitary in origin.

The effect on fat metabolism is to stimulate lipolysis of adipose tissue and the lipolytic effect of catecholamines, increasing the level of free fatty acids in the blood; due to their excessive intake into the liver and oxidation, the formation of ketone bodies increases. These effects of somatotropin are also classified as diabetogenic.

If an excess of the hormone occurs at an early age, gigantism is formed with proportional development of the limbs and trunk. An excess of the hormone in adolescence and adulthood causes increased growth of the epiphyseal areas of skeletal bones, areas with incomplete ossification, which is called acromegaly. . Internal organs also increase in size - splanchomegaly.

With congenital deficiency of the hormone, dwarfism is formed, called “pituitary dwarfism”. After the publication of J. Swift's novel about Gulliver, such people are colloquially called Lilliputians. In other cases, acquired hormone deficiency causes mild growth retardation.

Prolactin . The secretion of prolactin is regulated by hypothalamic peptides - the inhibitor prolactinostatin and the stimulator prolactoliberin. The production of hypothalamic neuropeptides is under dopaminergic control. The level of estrogen and glucocorticoids in the blood affects the amount of prolactin secretion

and thyroid hormones.

Prolactin specifically stimulates mammary gland development and lactation, but not its secretion, which is stimulated by oxytocin.

In addition to the mammary glands, prolactin affects the sex glands, helping to maintain the secretory activity of the corpus luteum and the formation of progesterone. Prolactin is a regulator of water-salt metabolism, reducing the excretion of water and electrolytes, potentiates the effects of vasopressin and aldosterone, stimulates the growth of internal organs, erythropoiesis, and promotes the manifestation of the maternal instinct. In addition to enhancing protein synthesis, it increases the formation of fat from carbohydrates, contributing to postpartum obesity.

Melanotropin . . It is formed in the cells of the intermediate lobe of the pituitary gland. Melanotropin production is regulated by hypothalamic melanoliberin. The main effect of the hormone is on the melanocytes of the skin, where it causes depression of pigment in the processes, an increase in free pigment in the epidermis surrounding the melanocytes, and an increase in melanin synthesis. Increases pigmentation of skin and hair.

Neurohypophysis, its connection with the hypothalamus. Effects of posterior pituitary hormones (oxygocin, ADH). The role of ADH in the regulation of fluid volume in the body. Diabetes insipidus.

Vasopressin . . It is formed in the cells of the supraoptic and paraventricular nuclei of the hypothalamus and accumulates in the neurohypophysis. The main stimuli that regulate the synthesis of vasopressin in the hypothalamus and its secretion into the blood by the pituitary gland can generally be called osmotic. They are represented by: a) an increase in the osmotic pressure of the blood plasma and stimulation of vascular osmoreceptors and osmoreceptor neurons of the hypothalamus; b) an increase in sodium content in the blood and stimulation of hypothalamic neurons that act as sodium receptors; c) a decrease in the central volume of circulating blood and blood pressure, perceived by volume receptors of the heart and mechanoreceptors of blood vessels;

d) emotional-painful stress and physical activity; e) activation of the renin-angiotensin system and the effect of angiotensin stimulating neurosecretory neurons.

The effects of vasopressin are realized due to the binding of the hormone in tissues to two types of receptors. Binding to Y1-type receptors, predominantly localized in the wall of blood vessels, through the second messengers inositol triphosphate and calcium causes vascular spasm, which contributes to the name of the hormone - “vasopressin”. Binding to Y2-type receptors in the distal parts of the nephron through the secondary messenger c-AMP ensures an increase in the permeability of the nephron collecting ducts to water, its reabsorption and urine concentration, which corresponds to the second name of vasopressin - “antidiuretic hormone, ADH”.

In addition to its effect on the kidney and blood vessels, vasopressin is one of the important brain neuropeptides involved in the formation of thirst and drinking behavior, memory mechanisms, and regulation of the secretion of adenopituitary hormones.

Lack or even complete absence of vasopressin secretion manifests itself in the form of a sharp increase in diuresis with the release of large amounts of hypotonic urine. This syndrome is called " diabetes insipidus", it can be congenital or acquired. Excess vasopressin syndrome (Parhon syndrome) manifests itself

in excessive fluid retention in the body.

Oxytocin . The synthesis of oxytocin in the paraventricular nuclei of the hypothalamus and its release into the blood from the neurohypophysis is stimulated by a reflex pathway when irritating the stretch receptors of the cervix and the receptors of the mammary glands. Estrogens increase the secretion of oxytocin.

Oxytocin causes the following effects: a) stimulates contraction of the smooth muscles of the uterus, promoting childbirth; b) causes contraction of smooth muscle cells of the excretory ducts of the lactating mammary gland, ensuring the release of milk; c) has a diuretic and natriuretic effect under certain conditions; d) participates in the organization of drinking and eating behavior; e) is an additional factor in the regulation of the secretion of adenopituitary hormones.

Depending on the location of receptors in target cells, hormones can be divided into three groups.

The first group consists lipid hormones. Being fat-soluble, they easily penetrate the cell membrane and interact with receptors localized inside the cell, usually in the cytoplasm.

Second group – protein and peptide hormones. They consist of amino acids and, compared to hormones of a lipid nature, have a higher molecular weight and are less lipophilic, which is why they pass through the plasma membrane with difficulty. The receptors for these hormones are located on the surface of the cell membrane, so that protein and peptide hormones do not penetrate the cell.

The third chemical group of hormones consists of low molecular weight thyroid hormones, formed by two amino acid residues linked by an ester bond. These hormones easily penetrate all cells of the body and interact with receptors localized in the nucleus. The same cell can have receptors of all three types, i.e. localized in the nucleus, cytosol and on the surface of the plasma membrane. In addition, different receptors of the same type may be present in the same cell; for example, receptors for various peptide and/or protein hormones may be located on the surface of the cell membrane.

Secondary messengers: 1) cyclic nucleotides (cAMP and cGMP); 2) Ca ions and 3) phosphatidylinositol metabolites.

Accession hormone to the receptor allows the latter to interact with the G protein. If a G protein activates the adenylate cyclase-cAMP system, it is called a Gs protein. Stimulation of adenylate cyclase, bound to the enzyme membrane through the Gs protein, catalyzes the conversion of a small amount of adenosine triphosphate present in the cytoplasm into cAMP inside the cell.

Next stage mediated activation of cAMP-dependent protein kinase, which phosphorylates specific proteins in the cell, triggering biochemical reactions, which guarantees the cell's response to the action of the hormone.

As soon as cAMP is formed in the cell, this ensures the sequential activation of a number of enzymes, i.e. cascade reaction. Thus, the first enzyme activated activates the second, which activates the third. The purpose of this mechanism is that a small number of molecules activated by adenylate cyclase can activate many more molecules in the next step of the cascade reaction, which is a way of amplifying the response.

Ultimately, thanks to this mechanism an insignificant amount of the hormone acting on the surface of the cell membrane triggers a powerful cascade of activating reactions.

If a hormone interacts with receptor, coupled to the inhibitory G-protein (Gi-protein), this reduces the formation of cAMP and, as a result, reduces cell activity.