Hormones and their mechanism of action. Regulation of vital functions of the body

The action of hormones is based on stimulation or inhibition of the catalytic function of certain enzymes in the cells of target organs. This action can be achieved by activating or inhibiting already existing enzymes. Moreover, an important role belongs to cyclic adenosine monophosphate(cAMP) which is here secondary intermediary(the role of the primary

the hormone itself acts as an intermediary). It is also possible to increase the concentration of enzymes by accelerating their biosynthesis through gene activation.

The mechanism of action of peptide and steroid hormones different. Amines and peptide hormones do not penetrate into the cell, but attach to specific receptors in the cell membrane on its surface. Receptor bound to enzyme adenylate cyclase. The hormone-receptor complex activates adenylate cyclase, which breaks down ATP to form cAMP. The action of cAMP is realized through a complex chain of reactions leading to the activation of certain enzymes through their phosphorylation, they carry out the final effect of the hormone (Fig. 2.3).

Rice. 2.4 Mechanism of action steroid hormones I - the hormone enters the cell and binds to a receptor in the cytoplasm; II - the receptor transports the hormone into the nucleus; III - the hormone interacts reversibly with the DNA of chromosomes; IV - the hormone activates the gene on which messenger RNA (mRNA) is formed; V-mRNA leaves the nucleus and initiates protein synthesis (usually an enzyme) on ribosomes; the enzyme realizes the final hormonal effect; 1 - cell membrane, 2 - hormone, 3 - receptor, 4 - nuclear membrane, 5 - DNA, 6 - mRNA, 7 - ribosome, 8 - protein (enzyme) synthesis.

Steroid hormones and Tk And T 4(thyroxine and triiodothyronine) are fat soluble, so they penetrate the cell membrane. The hormone binds to a receptor in the cytoplasm. The resulting hormone-receptor complex is transported to the cell nucleus, where it enters into a reversible interaction with DNA and induces the synthesis of a protein (enzyme) or several proteins. By turning on specific genes on a certain DNA section of one of the chromosomes, matrix (messenger) RNA (mRNA) is synthesized, which passes from the nucleus to the cytoplasm, attaches to ribosomes and induces protein synthesis here (Fig. 2.4).

Unlike enzyme-activating peptides, steroid hormones cause the synthesis of new enzyme molecules. In this regard, the effects of steroid hormones appear much more slowly than the effects of peptide hormones, but usually last longer.

2.2.5. Classification of hormones

Based on functional criteria, they distinguish three groups of hormones: 1) hormones that directly affect the target organ; these hormones are called effector 2) hormones, the main function of which is the regulation of the synthesis and release of effector hormones;

these hormones are called tropic 3) hormones produced nerve cells And regulating the synthesis and release of adenohypophysis hormones; These hormones are called releasing hormones, or liberins, if they stimulate these processes, or inhibitory hormones, statins, if they have the opposite effect. The close connection between the central nervous system and the endocrine system is carried out mainly with the help of these hormones.

In a complex system hormonal regulation organisms are distinguished more or less long chains regulation. Main line of interactions: CNS → hypothalamus → pituitary gland → peripheral endocrine glands. All elements of this system are united by feedback connections. The function of some endocrine glands is not under the regulatory influence of adenohypophysis hormones (for example, parathyroid glands, pancreas, etc.).

Hormones secreted by glands internal secretion, bind to plasma transport proteins or, in some cases, are adsorbed on blood cells and delivered to organs and tissues, affecting their function and metabolism. Some organs and tissues have a very high sensitivity to hormones, which is why they are called target organs or fabrics–targets. Hormones affect literally every aspect of metabolism, function and structure in the body.

According to modern concepts, the action of hormones is based on stimulation or inhibition of the catalytic function of certain enzymes. This effect is achieved by activating or inhibiting existing enzymes in cells by accelerating their synthesis through gene activation. Hormones can increase or decrease the permeability of cellular and subcellular membranes to enzymes and other biologically active substances, thereby facilitating or inhibiting the action of the enzyme.

The following types of mechanism of action of hormones are distinguished: membrane, membrane-intracellular and intracellular (cytosolic).

Diaphragm mechanism . The hormone binds to the cell membrane and, at the site of binding, changes its permeability to glucose, amino acids and some ions. In this case, the hormone acts as an effector of membrane transport. Insulin has this effect by changing glucose transport. But this type of hormone transport rarely occurs in isolated form. Insulin, for example, has both a membrane and membrane-intracellular mechanism of action.

Membrane-intracellular mechanism . Hormones act according to the membrane-intracellular type, which do not penetrate the cell and therefore affect metabolism through an intracellular chemical intermediary. These include protein-peptide hormones (hormones of the hypothalamus, pituitary gland, pancreas and parathyroid glands, thyrocalcitonin thyroid gland); derivatives of amino acids (hormones of the adrenal medulla - adrenaline and norepinephrine, thyroid hormones - thyroxine, triiodothyronine).

The functions of intracellular chemical messengers of hormones are performed by cyclic nucleotides - cyclic 3 ׳ ,5׳ – adenosine monophosphate (cAMP) and cyclic 3 ׳ ,5׳ – guanosine monophosphate (cGMP), calcium ions.

Hormones influence the formation of cyclic nucleotides: cAMP - through adenylate cyclase, cGMP - through guanylate cyclase.

Adenylate cyclase is built into the cell membrane and consists of 3 interconnected parts: receptor (R), represented by a set of membrane receptors located outside the membrane, conjugating (N), represented by a special N protein located in the lipid layer of the membrane, and catalytic (C), which is an enzymatic protein, that is, adenylate cyclase itself, which converts ATP (adenosine triphosphate) into cAMP.

Adenylate cyclase works according to the following scheme. As soon as the hormone binds to the receptor (R) and a hormone-receptor complex is formed, the N–protein–GTP (guanosine triphosphate) complex is formed, which activates the catalytic (C) part of adenylate ceclase. Activation of adenylate cyclase leads to the formation of cAMP inside the cell on the inner surface of the membrane from ATP.

Even one molecule of the hormone that binds to the receptor causes adenylate cyclase to work. In this case, for one molecule of bound hormone, 10-100 molecules of cAMP are formed inside the cell. Adenylate cyclase remains active as long as the hormone-receptor complex exists. Guanylate cyclase works in a similar way.

Inactive protein kinases are found in the cell cytoplasm. Cyclic nucleotides - cAMP and cGMP - activate protein kinases. There are cAMP-dependent and cGMP-dependent protein kinases that are activated by their cyclic nucleotide. Depending on the membrane receptor that binds a particular hormone, either adenylate ceclase or guanylate ceclase is switched on, and accordingly, either cAMP or cGMP is formed.

Most hormones act through cAMP, and only oxytocin, thyrocalcitonin, insulin and adrenaline act through cGMP.

With the help of activated protein kinases, two types of regulation of enzyme activity are carried out: activation of existing enzymes by covalent modification, that is, phospholation; changing the amount of enzyme protein due to changes in the rate of its biosynthesis.

The influence of cyclic nucleotides on biochemical processes stops under the influence of a special enzyme - phosphodiesterase, which destroys cAMP and cGMP. Another enzyme, phosphoprotein phosphase, destroys the result of the action of protein kinase, that is, it splits off phosphoric acid from enzyme proteins, as a result of which they become inactive.

There are very few calcium ions inside the cell; there are more outside the cell. They enter from the extracellular environment through calcium channels in the membrane. In the cell, calcium interacts with the calcium-binding protein calmodulin (CM). This complex changes the activity of enzymes, which leads to changes in the physiological functions of cells. The hormones oxytocin, insulin, and prostaglandin F 2α act through calcium ions. Thus, the sensitivity of tissues and organs to hormones depends on membrane receptors, and their specific regulatory effect is determined by an intracellular mediator.

Intracellular (cytosolic) mechanism of action . It is characteristic of steroid hormones (corticosteroids, sex hormones - androgens, estrogens and gestagens). Steroid hormones interact with receptors located in the cytoplasm. The resulting hormone-receptor complex is transferred to the nucleus and acts directly on the genome, stimulating or inhibiting its activity, i.e. acts on DNA synthesis, changing the rate of transcription and the amount of messenger RNA (mRNA). An increase or decrease in the amount of mRNA affects protein synthesis during translation, which leads to a change in the functional activity of the cell.

4 main metabolic regulation systems: Central nervous system(due to signal transmission through nerve impulses and neurotransmitters); Endocrine system(with the help of hormones that are synthesized in the glands and transported to target cells (in Fig. A); Paracrine and autocrine systems (with the participation of signaling molecules secreted from cells into the intercellular space - eicosanoids, histamines, gastrointestinal hormones, cytokines) (on Fig. B and C); Immune system (through specific proteins - antibodies, T-receptors, histocompatibility complex proteins.) All levels of regulation are integrated and act as a single whole.

The endocrine system regulates metabolism through hormones. Hormones (ancient Greek ὁρμάω - I excite, encourage) - - biologically active organic compounds, which are produced in small quantities in the endocrine glands, carry out humoral regulation of metabolism and have a different chemical structure.

Classic hormones have a number of characteristics: Distance of action - synthesis in the endocrine glands, and regulation of distant tissues Selectivity of action Strict specificity of action Short duration of action They act in very low concentrations, under the control of the central nervous system and the regulation of their action is carried out in most cases by feedback type They act indirectly through protein receptors and enzymatic systems

Organization of neurohormonal regulation There is a strict hierarchy or subordination of hormones. Maintaining hormone levels in the body in most cases provides a negative feedback mechanism.

Regulation of hormone levels in the body Changing the concentration of metabolites in target cells through a negative feedback mechanism suppresses hormone synthesis, acting either on the endocrine glands or the hypothalamus. There are endocrine glands for which there is no regulation by tropic hormones - a couple thyroid, medulla adrenal glands, renin-aldosterone system and pancreas. They are controlled by nervous influences or the concentration of certain substances in the blood.

Classification of hormones according to biological functions; by mechanism of action; By chemical structure; There are 4 groups: 1. Protein-peptide 2. Amino acid-derived hormones 3. Steroid hormones 4. Eicosanoids

1. Protein - peptide hormones Hormones of the hypothalamus; pituitary hormones; pancreatic hormones - insulin, glucagon; hormones of the thyroid and parathyroid glands - calcitonin and parathyroid hormone, respectively. They are produced mainly by targeted proteolysis. In hormones a short time life, have from 3 to 250 AMK residues.

The main anabolic hormone is insulin, the main catabolic hormone is glucagon.

Some representatives of protein-peptide hormones: thyroliberin (pyroglu-his-pro-NN HH 22), insulin and somatostatin.

2. Hormones are derivatives of amino acids. They are derivatives of the amino acid tyrosine. These include the thyroid hormones - triiodothyronine (II 33) and thyroxine (II 44), as well as adrenaline and norepinephrine - catecholamines.

3. Hormones of steroid nature Synthesized from cholesterol (in Fig.) Hormones of the adrenal cortex - corticosteroids (cortisol, corticosterone) Hormones of the adrenal cortex - mineralocorticoids (andosterone) Sex hormones: androgens (19 “C”) and estrogens (18 “C” )

Eicosanoids The precursor of all eicosanoids is arachidonic acid. They are divided into 3 groups - prostaglandins, leukotrienes, thromboxanes. Eikazonoids are mediators (local hormones) - a widespread group of signaling substances that are formed in almost all cells of the body and have a short range of action. This is how they differ from classical hormones synthesized in special cells of the endocrine glands. .

Characteristic different groups eikasonoids Prostaglandins (Pg) - are synthesized in almost all cells, except erythrocytes and lymphocytes. The following types of prostaglandins are distinguished: A, B, C, D, E, F. The functions of prostaglandins are reduced to changing the tone of the smooth muscles of the bronchi, genitourinary and vascular systems, gastrointestinal tract, while the direction of changes varies depending on the type of prostaglandins and conditions. They also affect body temperature. Prostacyclins are a subtype of prostaglandins (Pg I), but additionally have a special function - they inhibit platelet aggregation and cause vasodilation. They are especially actively synthesized in the endothelium of the vessels of the myocardium, uterus, and gastric mucosa. .

Thromboxanes and leukotrienes Thromboxanes (Tx) are formed in platelets, stimulate their aggregation and cause constriction small vessels. Leukotrienes (Lt) are actively synthesized in leukocytes, in the cells of the lungs, spleen, brain, and heart. There are 6 types of leukotrienes: A, B, C, D, E, F. In leukocytes, they stimulate motility, chemotaxis and migration of cells to the site of inflammation. They also cause contraction of the bronchial muscles in doses 100-1000 times less than histamine.

Interaction of hormones with target cell receptors For manifestation biological activity The binding of hormones to receptors should result in a signal that triggers a biological response. For example: the thyroid gland is a target for thyrotropin, under the influence of which the number of acinar cells increases and the rate of synthesis of thyroid hormones increases. Target cells distinguish the corresponding hormone due to the presence of the corresponding receptor.

General characteristics of receptors Receptors can be located: - on the surface of the cell membrane - inside the cell - in the cytosol or in the nucleus. Receptors are proteins that can consist of several domains. Membrane receptors have a hormone recognition and binding domain, a transmembrane and a cytoplasmic domain. Intracellular (nuclear) – hormone binding domains, DNA and protein binding domains that regulate transduction.

The main stages of hormonal signal transmission: through membrane (hydrophobic) and intracellular (hydrophilic) receptors. These are the fast and slow ways.

The hormonal signal changes the rate of metabolic processes by: - ​​changing the activity of enzymes - changing the number of enzymes. According to the mechanism of action, hormones are distinguished: - interacting with membrane receptors (peptide hormones, adrenaline, eicosanoids) and - interacting with intracellular receptors (steroid and thyroid hormones)

Transmission of hormonal signals through intracellular receptors for steroid hormones (adrenocortical hormones and sex hormones), thyroid hormones (T 3 and T 4). Slow transmission type.

Transmission of a hormonal signal through membrane receptors The transmission of information from the primary messenger of the hormone occurs through the receptor. The receptors transform this signal into a change in concentration secondary intermediaries, called secondary messengers. The coupling of the receptor with the effector system is carried out through the GG protein. General mechanism, through which biological effects are realized is the process of “phosphorylation - dephosphorylation of enzymes” There are different mechanisms transmission of hormonal signals through membrane receptors - adenylate cyclase, guanylate cyclase, inositol phosphate systems and others.

The signal from the hormone is transformed into a change in the concentration of secondary messengers - c. AMF, c. GTP, IF 3, DAG, CA 2+, NO.

The most common system for transmitting hormonal signals through membrane receptors is the adenylate cyclase system. The hormone-receptor complex is associated with a G protein, which has 3 subunits (α, β and γ). In the absence of the hormone, the α subunit is associated with GTP and adenylate cyclase. The hormone-receptor complex leads to the cleavage of the βγ dimer from α GTP. The α subunit of GTP activates adenylate cyclase, which catalyzes the formation of cyclic AMP (c. AMP). c. AMP activates protein kinase A (PKA), which phosphorylates enzymes that change the rate of metabolic processes. Protein kinases are classified as A, B, C, etc.

Adrenaline and glucagon, through the adenylate cyclase hormonal signal transmission system, activate hormone-dependent adipocyte TAG lipase. Occurs when the body is stressed (fasting, prolonged muscle work, cooling). Insulin blocks this process. Protein kinase A phosphorylates TAG lipase and activates it. TAG lipase cleaves fatty acids from triacylglycerols to form glycerol. Fatty acid oxidize and provide the body with energy.

Signal transmission from adrenergic receptors. AC – adenylate cyclase, Pk. A – protein kinase A, Pk. C – protein kinase C, Fl. C – phospholipase C, Fl. A 2 – phospholipase A 2, Fl. D – phospholipase D, PC – phosphatidylcholine, PL – phospholipids, FA – phosphatidic acid, Ach. K – arachidonic acid, PIP 2 – phosphatidylinositol biphosphate, IP 3 – inositol triphosphate, DAG – diacylglycerol, Pg – prostaglandins, LT – leukotrienes.

Adrenergic receptors of all types realize their action through Gs proteins. The α-subunits of this protein activate adenylate cyclase, which ensures the synthesis of c in the cell. AMP from ATP and activation of c. AMP-dependent protein kinase A. The ββ γ-subunit of the Gs protein activates L-type Ca 2+ channels and maxi-K+ channels. Under the influence of c. AMP-dependent protein kinase A phosphorylates myosin light chain kinase and it becomes inactive, unable to phosphorylate myosin light chains. The process of phosphorylation of light chains stops and the smooth muscle cell relaxes.

American scientists Robert Lefkowitz and Brian Kobilka were awarded Nobel Prize in 2012 for understanding the mechanisms of interaction of adrenaline receptors with G-proteins. Interaction of the beta-2 receptor (indicated in blue) with G-proteins (indicated in green). G protein-coupled receptors are very beautiful if we consider the architectural molecular assemblies of the cell as masterpieces of nature. They are called "semi-spiral" because they are helically packed into cell membrane in the manner of a Christmas tree serpentine and “pierce” it seven times, exposing to the surface a “tail” capable of receiving a signal and transmitting conformational changes to the entire molecule.

G proteins are a family of proteins that belong to GTPases and function as intermediaries in intracellular signaling cascades. G proteins are so named because in their signaling mechanism they use the replacement of GDP ( Blue colour) to GTF ( green color) as a molecular functional “switch” for regulating cellular processes.

G proteins are divided into two main groups - heterotrimeric (“large”) and “small”. Heterotrimeric G proteins are proteins with a quaternary structure, consisting of three subunits: alpha (α), beta (β) and gamma (γ). Small G-proteins are proteins from one polypeptide chain; they have a molecular weight of 20-25 k. And they belong to the Ras superfamily of small GTPases. Their single polypeptide chain is homologous to the α subunit of heterotrimeric G proteins. Both groups of G proteins are involved in intracellular signaling.

Cyclic adenosine monophosphate (cyclic AMP, c. AMP, c. AMP) is an ATP derivative that acts as a secondary messenger in the body, used for the intracellular distribution of signals of certain hormones (for example, glucagon or adrenaline) that cannot pass through the cell membrane. .

Each of the hormonal signal transmission systems corresponds to a specific class of protein kinases. The activity of type A protein kinases is regulated by c. AMP, protein kinase G - c. GMF. Ca 2+ - calmodulin-dependent protein kinases are controlled by the concentration of CA 2+. Type C protein kinases are regulated by DAG. An increase in the level of any second messenger leads to the activation of a certain class of protein kinases. Sometimes a membrane receptor subunit may have enzyme activity. For example: insulin receptor tyrosine protein kinase, whose activity is regulated by the hormone.

The action of insulin on target cells begins after it binds to membrane receptors, and the intracellular domain of the receptor has tyrosine kinase activity. Tyrosine kinase triggers the phosphorylation of intracellular proteins. The resulting autophosphorylation of the receptor leads to an increase in the primary signal. The insulin receptor complex can cause activation of phospholipase C, formation of second messengers inositol triphosphate and diacylglycerol, activation of protein kinase C, inhibition of c. AMF. The involvement of several second messenger systems explains the diversity and differences in the effects of insulin in different tissues.

Another system is the guanylate cyclase messenger system. The cytoplasmic domain of the receptor has guanylate cyclase (heme-containing enzyme) activity. Molecules c. GTP can activate ion channels or protein kinase GG, which phosphorylate enzymes. c. GMP controls water exchange and ion transport in the kidneys and intestines, and serves as a relaxation signal in the heart muscle.

Inositol phosphate system. The binding of a hormone to a receptor causes a change in the conformation of the receptor. Dissociation of the G-G protein occurs and GDP is replaced by GTP. The separated α-subunit associated with the GTP molecule acquires an affinity for phospholipase C. Under the action of phospholipase-C, the membrane lipid phosphatidylinositol-4, 5-bisphosphate (PIP 2) is hydrolyzed and inositol-1, 4, 5-triphosphate (IP 3) is formed ) and diacylglycerol (DAG). DAG is involved in the activation of the enzyme protein kinase C (PKC). Inositol-1, 4, 5-triphosphate (IP 3) binds to specific centers of the Ca 2+ channel of the ER membrane, this leads to a change in protein conformation and opening of the channel - Ca 2+ enters the cytosol. In the absence of IF in the cytosol, channel 3 is closed.

The pathways of action of hormones are considered as two alternative possibilities:

1) the action of the hormone from the surface of the cell membrane after binding to a specific membrane receptor and thereby triggering a chain of biochemical transformations in the membrane and cytoplasm (effects of peptide hormones and catecholamines);

2) the action of the hormone by penetration through the membrane and binding to the cytoplasmic receptor, after which the hormone-receptor complex penetrates into the nucleus and organelles of the cell, where it realizes its regulatory effect (steroid hormones, thyroid hormones).

Guanylate cyclase-cGMP system

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 oxidative systems of membranes. Typical stimulation of guanylate cyclase activity by acetylcholine is also realized indirectly through Ca++. Through activation of guanylate cyclase, the effect of atrial natriuretic hormone, atriopeptide, is realized. By activating peroxidation, it stimulates gu-anylate cyclase biologically active substance (tissue hormone) vascular wall- relaxing endothelial factor. 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 plays a role in the hyperpolarization of retinal receptors under the influence of photons of light. Enzymatic hydrolysis of cGMP is carried out using a specific phosphodiesterase.

TICKET No. 8

The role of parathyroid hormone and calcitonin in the regulation of calcium levels in the blood. Chemical origin, mechanisms of action, target organs, metabolic effects. Pathologies associated with hyper- and hypofunction of these hormones.

Parathyroid hormone- a polypeptide consisting of 84 amino acid residues, is formed and secreted by the parathyroid glands in the form of a high molecular weight prohormone. After leaving the cells, the prohormone undergoes proteolysis to form parathyroid hormone. The production, secretion and hydrolytic cleavage of parathyroid hormone regulates the concentration of calcium in the blood. Reducing it leads to stimulation of synthesis and release of the hormone, and decreasing it causes the opposite effect. Parathyroid hormone increases the concentration of calcium and phosphate in the blood. Parathyroid hormone acts on osteoblasts, causing increased demineralization of bone tissue. Not only the hormone itself is active, but also its amino-terminal peptide (1-34 amino acids). It is formed during the hydrolysis of parathyroid hormone in hepatocytes and kidneys in those more the lower the calcium concentration in the blood. Enzymes that destroy intermediate bone substance are activated in osteoclasts, and reverse reabsorption of phosphates is inhibited in the cells of the proximal tubules of the kidneys. Calcium absorption increases in the intestines.

Calcitonin- a hypocalcemic hormone of peptide nature, synthesized in C-cells (parafollicular cells) of the thyroid gland. A certain amount is synthesized from the lungs. For the first time, the existence of calcitonin, which has the ability to maintain a constant level of calcium in the blood, was pointed out in 1962 by D. Knopp, who mistakenly believed that this hormone is synthesized by the parathyroid glands.
The main targets of the hormone's action are bones and kidneys. Main physiological role calcitonin is to prevent hypercalcemia, which is possible when calcium enters the body. This function is most likely carried out by inhibiting the release of calcium from the bones.
The main function of this hormone is its antagonistic effect on parathyroid hormone (a hormone produced by the parathyroid glands, which is also involved in the regulation of calcium metabolism and increases calcium levels in the blood. See "Parathormone"). The effects of calcitonin and parathyroid hormone on bones are generally opposite, but at the same time it is not an antiparathyroid hormone. These hormones likely act on different types of cells in the bones.
The regulation of calcitonin synthesis is controlled by the concentration of calcium in the blood. An increase in calcium concentration stimulates hormone synthesis, a decrease leads to reverse effect. The effect of calcitonin is manifested in inhibiting the activity of osteoclasts, reducing bone resorption, preventing the release of calcium from the bone and, as a consequence, reducing the calcium level in the blood. Calcitonin has a direct effect on the kidneys, increasing the excretion of calcium, phosphorus and sodium by inhibiting their tubular reabsorption. Calcitonin inhibits the absorption of calcium into small intestine.
IN clinical practice determination of calcitonin content in the blood may have important for the diagnosis of medullary thyroid cancer, since its content in the blood serum increases in this form of cancer. It should be taken into account that an increase in the level of calcitonin in the blood can occur when lung cancer and breast and tumors of other locations (prostate cancer). Some increase in the content is possible during pregnancy, estrogen treatment, calcium administration, vitamin D overdose. Therefore, the diagnosis is made taking into account all possible methods examinations.

Target organs for PTH - bones and kidneys. Specific receptors are localized in kidney and bone cells that interact with parathyroid hormone, resulting in a cascade of events that initiates, leading to the activation of adenylate cyclase. Inside the cell, the concentration of cAMP molecules increases, the action of which stimulates the mobilization of calcium ions from intracellular reserves. Calcium ions activate kinases that phosphorylate specific proteins that induce transcription of specific genes.

Hyperparathyroidism

At primary hyperparathyroidism the mechanism of suppression of parathyroid hormone secretion in response to hypercalcemia is disrupted. This disease occurs with a frequency of 1:1000. The causes may be a tumor of the parathyroid gland (80%) or diffuse glandular hyperplasia, in some cases parathyroid cancer (less than 2%). Excessive secretion of parathyroid hormone leads to increased mobilization of calcium and phosphate from bone tissue, increased reabsorption of calcium and excretion of phosphate in the kidneys. As a result, hypercalcemia occurs, which can lead to a decrease in neuromuscular excitability and muscle hypotonia. Patients develop general and muscle weakness, fatigue and pain in certain muscle groups, the risk of spinal fractures increases, femur and bones of the forearm. Increased concentration of phosphate and calcium ions in renal tubules can cause the formation of kidney stones and leads to hyperphosphaturia and hypophosphatemia.

Secondary hyperparathyroidism occurs in chronic renal failure and vitamin D 3 deficiency and is accompanied by hypocalcemia, mainly associated with impaired calcium absorption in the intestine due to inhibition of calcitriol formation by affected kidneys. In this case, the secretion of parathyroid hormone increases. However increased level parathyroid hormone cannot normalize the concentration of calcium ions in the blood plasma due to impaired calcitriol synthesis and reduced calcium absorption in the intestine. Along with hypocalcemia, hyperfostatemia is often observed. Patients develop skeletal damage (osteoporosis) due to increased mobilization of calcium from bone tissue. In some cases (with the development of adenoma or hyperplasia parathyroid glands) autonomous hypersecretion of parathyroid hormone compensates for hypocalcemia and leads to hypercalcemia ( tertiary hyperparathyroidism).

Hypoparathyroidism

The main symptom of hypoparathyroidism caused by insufficiency parathyroid glands, - hypocalcemia. A decrease in the concentration of calcium ions in the blood can cause neurological, ophthalmological and cardiovascular disorders, as well as lesions connective tissue. In a patient with hypoparathyroidism, an increase in neuromuscular conduction, attacks of tonic convulsions, convulsions respiratory muscles and diaphragm, laryngospasm

Deciphering the mechanisms of action of hormones in animals provides an opportunity to better understand physiological processes - regulation of metabolism, protein biosynthesis, growth and differentiation of tissues.

This is also important from a practical point of view, due to the increasingly widespread use natural and synthetic hormonal drugs in animal husbandry and veterinary medicine.

Currently, there are about 100 hormones that are formed in the endocrine glands, enter the blood and have a diverse effect on metabolism in cells, tissues and organs. It is difficult to identify physiological processes in the body that are not under the regulatory influence of hormones. Unlike many enzymes that cause individual, narrowly targeted changes in the body, hormones have multiple effects on metabolic processes and other physiological functions. At the same time, none of the hormones, as a rule, completely provides regulation individual functions. This requires the influence of a number of hormones in a certain sequence and interaction. For example, somatotropin stimulates growth processes only when active participation insulin and thyroid hormones. The growth of follicles is mainly ensured by follitropin, and their maturation and the process of ovulation are carried out under the regulating influence of lutropin, etc.

Most hormones in the blood are bound to albumins or globulins, which protects them from rapid destruction by enzymes and maintains optimal concentrations of metabolically active hormones in cells and tissues. Hormones have a direct effect on the process of protein biosynthesis. Steroid and protein hormones (sex hormones, triple pituitary hormones) in target tissues cause an increase in the number and volume of cells. Other hormones, such as insulin, gluco- and mineralocorticoids, affect protein synthesis indirectly.

The first link physiological action Hormones in the animal body are cell membrane receptors. In the same cells there are large quantities several types; specific receptors, with the help of which they selectively bind molecules of various hormones circulating in the blood. For example, fat cells in their membranes they have specific receptors for glucagon, lutropin, thyrotropin, corticotropin.

Most hormones of a protein nature, due to the large size of their molecules, cannot penetrate cells, but are located on their surface and, interacting with the corresponding receptors, affect the metabolism inside the cells. Thus, in particular, the effect of thyrotropin is associated with the fixation of its molecules on the surface of thyroid cells, under the influence of which the permeability of cell membranes to sodium ions increases, and in their presence the intensity of glucose oxidation increases. Insulin increases the permeability of cell membranes in tissues and organs for glucose molecules, which helps reduce its concentration in the blood and transfer to tissues. Somatotropin also has a stimulating effect on the synthesis of nucleic acids and proteins by acting on cell membranes.

The same hormones can influence metabolic processes in tissue cells in various ways. Along with the change in permeability cell membranes and membranes of intracellular structures for various enzymes and others chemical substances, under the influence of the same hormones, the ionic composition of the environment outside and inside cells, as well as the activity of various enzymes and the intensity of metabolic processes, can change.

Hormones influence the activity of enzymes and the gene apparatus of cells not directly, but with the help of mediators (intermediaries). One of these mediators is cyclic 3′, 5′-adenosine monophosphate (cyclic AMP). Cyclic AMP (cAMP) is formed inside cells from adenosine triphosphoric acid (ATP) with the participation of the enzyme adenyl cyclase located on the cell membrane, which is activated when exposed to the corresponding hormones. On the intracellular membranes there is an enzyme phosphodiesterase, which converts cAMP into a less active substance - 5′-adenosine monophosphate and thereby stops the effect of the hormone.

When a cell is exposed to several hormones that stimulate the synthesis of cAMP in it, the reaction is catalyzed by the same adenyl cyclase, but the receptors in cell membranes for these hormones are strictly specific. Therefore, for example, corticotropin affects only the cells of the adrenal cortex, and thyrotropin affects the cells of the thyroid gland, etc.

Detailed studies have shown that the action of most protein and peptide hormones leads to stimulation of adenyl cyclase activity and an increase in the concentration of cAMP in target cells, which is associated with further transmission of information hormonal effects with the active participation of a number of protein kinases. cAMP plays the role of an intracellular mediator of the hormone, ensuring an increase in the activity of protein kinases dependent on it in the cytoplasm and nuclei of cells. In turn, cAMP-dependent protein kinases catalyze the phosphorylation of ribosomal proteins, which is directly related to the regulation of protein synthesis in target cells under the influence of peptide hormones.

Steroid hormones, catecholamines, and thyroid hormones, due to their small molecular sizes, pass through the cell membrane and interact with cytoplasmic receptors inside the cells. Subsequently, steroid hormones, in combination with their receptors, which are acidic proteins, pass into the cell nucleus. It is assumed that peptide hormones, as hormone-receptor complexes are split, also act on specific receptors in the cytoplasm, Golgi complex and nuclear membrane.

Not all hormones stimulate the activity of the enzyme adenyl cyclase and an increase in its concentration in cells. Some peptide hormones, in particular insulin, ocytocin, calcitonin, have an inhibitory effect on adenyl cyclase. The physiological effect of their action is believed to be due not to an increase in the concentration of cAMP, but to its decrease. At the same time, in cells that have specific sensitivity to the mentioned hormones, the concentration of another cyclic nucleotide, cyclic guanosine monophosphate (cGMP), increases. The result of the action of hormones in the cells of the body ultimately depends on the influence of both cyclic nucleotides - cAMP and cGMP, which are universal intracellular mediators - hormone intermediaries. With regard to the action of steroid hormones, which, in combination with their receptors, penetrate the cell nucleus, the role of cAMP and cGMP as intracellular mediators is considered questionable.

Many, if not all, hormones are finite physiological effect manifest indirectly - through changes in the biosynthesis of enzyme proteins. Protein biosynthesis is a complex multi-stage process carried out with the active participation of the cell's gene apparatus.

The regulatory effect of hormones on protein biosynthesis is carried out mainly by stimulating the RNA polymerase reaction with the formation of ribosomal and nuclear RNA species, as well as messenger RNA and by influencing functional activity ribosomes and other parts of protein metabolism. Specific protein kinases in cell nuclei stimulate phosphorylation of the corresponding protein components and the RNA polymerase reaction with the formation of messenger RNAs encoding the synthesis of proteins in cells and target organs. At the same time, in the nuclei of cells, genes are derepressed, which are released from the inhibitory effect of specific repressors - nuclear histone proteins.

Hormones such as estrogens and androgens in the nuclei of cells bind to histone proteins that repress the corresponding genes, and thereby bring the gene apparatus of the cells into active functional state. At the same time, androgens influence the gene apparatus of cells less than estrogens, which is due to a more active connection of the latter with chromatin and a weakening of RNA synthesis in the nuclei.

Along with the activation of protein synthesis in cells, the formation of histone proteins occurs, which are repressors of gene activity, and this prevents metabolic functions nuclei and excessive growth stimulation. Consequently, cell nuclei have their own mechanism for genetic and mitotic regulation of metabolism and growth.

Due to the influence of hormones on anabolic processes in the body, retention increases nutrients feed and, consequently, the amount of substrates for interstitial metabolism increases, the regulatory mechanisms of biochemical processes associated with more effective use nitrogenous and other compounds.

The processes of protein synthesis in cells are influenced by somatotropin, corticosteroids, estrogens, and thyroxine. These hormones stimulate the synthesis of various messenger RNAs and thereby enhance the synthesis of the corresponding proteins. In the processes of protein synthesis, insulin also plays an important role, which stimulates the binding of messenger RNAs to ribosomes and, consequently, activates protein synthesis. By activating the chromosomal apparatus of cells, hormones influence an increase in the rate of protein synthesis and the concentration of enzymes in the cells of the liver and other organs and tissues. However, the mechanism of the influence of hormones on intracellular metabolism has not yet been sufficiently studied.

The action of hormones, as a rule, is closely related to the functions of enzymes that ensure biochemical processes in cells, tissues and organs. Hormones are involved in biochemical reactions as specific activators or inhibitors of enzymes, exerting their influence on enzymes by ensuring their connection with various biocolloids.

Since enzymes are protein bodies, the effect of hormones on their functional activity is manifested primarily by influencing the biosynthesis of enzymes and catabolic coenzyme proteins. One of the manifestations of the activity of hormones is their participation in the interaction of a number of enzymes in various parts of complex reactions and processes. As is known, vitamins play a certain role in the construction of coenzymes. It is believed that hormones also perform a regulatory function in these processes. For example, corticosteroids affect the phosphorylation of some B vitamins.

Particularly important for prostaglandins is their high physiological activity and very low side effect. It is now known that prostaglandins act like mediators inside cells and play important role in realizing the effect of hormones. At the same time, the processes of synthesis of cyclic adenosine monophosphate (cAMP), which is capable of transmitting the narrowly targeted effect of hormones, are activated. It is possible to assume that pharmacological substances act inside cells through the production of specific prostaglandins. Now in many countries the mechanism of action of prostaglandins is being studied at the cellular and molecular level, since a comprehensive study of the action of prostaglandins can make it possible to specifically influence metabolism and other physiological processes in the body of animals.

Based on the foregoing, we can conclude that hormones have a complex and diverse effect in the body of animals. The complex influence of nervous and humoral regulation ensures a coordinated course of all biochemical and physiological processes. However, the finest details of the mechanism of action of hormones have not yet been sufficiently studied. This problem interests many scientists and is of great interest for the theory and practice of endocrinology, as well as animal husbandry and veterinary medicine.