The mechanism of action of the hormones of the pituitary and hypothalamus

Hormonal regulation begins with the process of synthesis and secretion of hormones in the glands of internal secretion. They are functionally interrelated and represent a single whole. The process of biosynthesis of hormones, carried out in specialized cells, proceeds spontaneously and is fixed genetically. Genetic control of the biosynthesis of most protein-peptide hormones, particularly adenohypophysotropic hormones, occurs most often directly in the polysomes of hormone precursors or at the level of mRNA formation of the hormone itself, whereas the biosynthesis of the hormones of the hypothalamus is accomplished by the formation of mRNA of enzyme proteins regulating various stages of hormone formation, t e., an extra-bisomal synthesis occurs. Formation of the primary structure of hormones of protein-peptide nature is the result of direct translation of the nucleotide sequences of the corresponding mRNA synthesized on the active parts of the genome of hormone-producing cells. The structure of most protein hormones or their precursors is formed in polysomes according to the general scheme of protein biosynthesis. Note that the possibility of synthesis and translation of the mRNA of a given hormone or its precursors is specific for a nuclear device and a polysome of a certain type of cells. Thus, STH is synthesized in small eosinophils of adenohypophysis, prolactin - in large eosinophilic, and gonadotropins - in special basophilic cells. The biosynthesis of TRH and LH-RG in the cells of the hypothalamus is somewhat different. These peptides are formed not in polysomes on the mRNA matrix, but in the soluble part of the cytoplasm under the influence of the corresponding synthetase systems.

The direct translation of genetic material in cases of the isolation of most polypeptide hormones often leads to the formation of low-activity precursors - polypeptide pre-hormones (prehormones). Biosynthesis of polypeptide hormone consists of two different stages: ribosomal synthesis of the inactive precursor on the mRNA matrix and post-translational formation of the active hormone. The first stage proceeds necessarily in the cells of the adenohypophysis, the second one can also be carried out outside it.

Post-translational activation of hormonal precursors is possible in two ways: by multi-step enzymatic degradation of molecules of translocated large-molecule precursors with a decrease in the size of the activated hormone molecule and due to the non-enzymatic association of pro-hormonal subunits with enlargement of the molecule size of the activated hormone.

In the first case, posttranslational activation is characteristic for ACTH, beta-lipotropin, and in the second case for glycoprotein hormones, in particular gonadotropins and TSH.

Sequential activation of protein-peptide hormones has a direct biological meaning. First, while limiting the hormonal effects in the place of education; Secondly, optimal conditions are provided for the manifestation of polyfunctional regulatory effects with minimal use of genetic and building material, and also the cellular transport of hormones is facilitated.

The release of hormones occurs, as a rule, spontaneously, and not continuously and evenly, but impulsively, in separate discrete portions. This is due, apparently, to the cyclic nature of the processes of biosynthesis, intracellular deposition and transport of hormones. Under physiological conditions, the secretory process must provide a certain basal level of hormones in circulating fluids. This process, like biosynthesis, is controlled by specific factors. The secretion of pituitary hormones is primarily determined by the corresponding releasing hormones of the hypothalamus and the level of circulating hormones in the blood. The formation of the hypothalamic releasing hormones themselves depends on the effect of the adrenergic or cholinergic neurotransmitters, as well as the concentration of the target hormones in the blood.

Biosynthesis and secretion are closely interrelated. The chemical nature of the hormone and the specific mechanisms of its secretion determine the degree of conjugation of these processes. So, this indicator is maximum in case of secretion of steroid hormones, which diffuse relatively freely through cell membranes. The magnitude of conjugation of biosynthesis and secretion of protein-peptide hormones and catecholamines is minimal. These hormones are released from the cellular secretory granules. Intermediate position on this indicator is occupied by thyroid hormones, which are secreted by releasing them from a protein-bound form.

Thus, it should be emphasized that the synthesis and secretion of the hormones of the pituitary and hypothalamus are carried out to a certain extent separately.

The main structural and functional element of the secretory process of protein-peptide hormones are secretory granules or vesicles. These are special morphological formations of ovoid form of various sizes (100-600 nm), surrounded by a thin lipoprotein membrane. Secretory granules of hormone-producing cells arise from the Golgi complex. Its elements surround the prohormone or hormone, gradually forming granules, which perform a number of interrelated functions in the system of processes responsible for the secretion of hormones. They can be the site of activation of peptide prohormones. The second function that granules perform is storage of hormones in the cell until the specific secretory stimulus is exposed. The granule membrane limits the release of hormones into the cytoplasm and protects the hormones from the action of cytoplasmic enzymes that can inactivate them. The specific substances and ions contained in the granules have a certain significance in the mechanisms of deposition. These include proteins, nucleotides, ions, the main purpose of which is the formation of non-covalent complexes with hormones and prevention of their penetration through the membrane. Secretory granules have another very important quality - the ability to move to the periphery of the cell and transport the hormones deposited in them to the plasma membranes. The movement of the granules is carried out inside the cells with the participation of cell organelles - microfilaments (their diameter is 5 nm), built of actin protein, and hollow microtubes (diameter 25 nm), consisting of a complex of contractile proteins tubulin and dynein. In case of need for blockade of secretory processes, drugs that destroy microfilaments or dissociate microtubules (cytochalasin B, colchicine, vinblastine) are usually used. Intracellular transport of granules requires the expenditure of energy and the presence of calcium ions. Membranes of granules and plasma membranes with the participation of calcium come into contact with each other, and the secret is released into the extracellular space through the "pores" formed in the cell membrane. This process is called exocytosis. Devastated granules can in some cases be reconstructed and returned to the cytoplasm.

The starting point in the secretion of protein-peptide hormones is increased formation of AMP (cAMP) and an increase in the intracellular concentration of calcium ions that penetrate the plasma membrane and stimulate the transfer of hormonal granules to the cell membrane. The processes described above are regulated both intracellularly and extracellularly. If the intracellular regulation and self-regulation of the hormone-producing functions of the pituitary and hypothalamic cells are largely limited, the systemic control mechanisms ensure the functional activity of the pituitary and hypothalamus in accordance with the physiological state of the organism. Violation of regulatory processes can lead to a serious pathology of gland functions and, consequently, of the whole organism.

Regulatory influences can be divided into stimulating and inhibitory. At the heart of all regulatory processes is the principle of feedback. The leading place in the ordering of hormonal functions of the pituitary gland belongs to the structures of the central nervous system, and primarily to the hypothalamus. Thus, the physiological mechanisms controlling the activity of the pituitary gland can be divided into nerve and hormonal.

Considering the processes of regulation of synthesis and secretion of pituitary hormones, we should first of all point to the hypothalamus with its ability to synthesize and secrete neurohormones - releasing hormones. As indicated, the regulation of adenohypophyseal hormones is carried out with the help of releasing hormones synthesized in certain nuclei of the hypothalamus. The small cell elements of these hypothalamic structures have conductive paths that contact the vessels of the primary capillary network, through which the releasing hormones act, reaching the adenohypophyseal cells.

Considering the hypothalamus as a neuroendocrinal center, i.e., as the place of transformation of the nerve impulse into a specific hormonal signal, which carriers are the releasing hormones, scientists are exploring the possibility of the influence of various mediator systems directly on the processes of synthesis and secretion of adenohypophysial hormones. With the help of improved methodological methods, researchers have identified, for example, the role of dopamine in the regulation of the secretion of a number of tropic hormones of the adenohypophysis. In this case, dopamine appears not only as a neurotransmitter regulating the function of the hypothalamus, but also as a releasing hormone, which takes part in the regulation of the function of the adenohypophysis. Similar data were obtained for norepinephrine, which is involved in the control of ACTH secretion. The fact of a dual control of the synthesis and secretion of adeno-pituitary-hormones is now established. The main point of application of various neurotransmitters in the system of regulation of hypothalamic releasing hormones are the structures of the hypothalamus in which they are synthesized. At present, the spectrum of physiologically active substances involved in the regulation of hypothalamic neurohormones is quite wide. These are classical neurotransmitters of the adrenergic and cholinergic nature, of a number of amino acids, substances with a morphine-like action - endorphins and enkephalins. These substances are the main link between the central nervous system and the endocrine system, which ultimately ensures their unity in the body. Functional activity of the hypothalamic neuroendocrine cells can be directly controlled by various parts of the brain with the help of nerve impulses coming through various afferent ways.

Recently, in neuroendocrinology, another problem has arisen - the study of the functional role of releasing hormones localized in other structures of the central nervous system, outside the hypothalamus and not directly related to the hormonal regulation of adenohypophysis functions. It has been experimentally confirmed that they can be considered both as neurotransmitters and as neuromodulators of a number of systemic processes.

In the hypothalamus, the releasing hormones are localized in certain regions or nuclei. For example, LH-RG is localized in the anterior and mediobasal hypothalamus, TRH in the middle hypothalamus, KRG mainly in its posterior regions. This also does not exclude the diffuse distribution in the gland of neurohormones.

The main function of adenohypophyseal hormones is to activate a number of peripheral endocrine glands (adrenal cortex, thyroid gland, gonads). Tropic hormones of the pituitary - ACTH, TTG, LH and FSH, STH - cause specific responses. Thus, the first causes the growth (hypertrophy and hyperplasia) of the bundle zone of the adrenal cortex and the enhancement in its cells of the synthesis of glucocorticoids; the second is the main regulator of morphogenesis of the follicular apparatus of the thyroid gland, various stages of synthesis and secretion of thyroid hormones; LH is the main stimulator of ovulation and formation of the yellow body in the ovaries, growth of interstitial cells in the testes, synthesis of estrogens, progestins and gonadal androgens; FSH causes an acceleration of the growth of ovarian follicles, sensitizes them to the action of LH, and also activates spermatogenesis; STG, acting in a stimulating manner for liver secretion of somatomedins, determines the linear growth of the body and anabolic processes; LTG promotes the manifestation of the action of gonadotropins.

It should also be noted that the tropic hormones of the pituitary gland, showing its effect as regulators of the functions of the peripheral endocrine glands, are often able to have a direct effect. So, for example, ACTH as the main regulator of synthesis of glucocorticoids gives a number of extradrenal effects, in particular lipolytic and melanocyte-stimulating.

Hormones of hypothalamic-pituitary origin, i.e. Protein-peptide, very quickly disappear from the blood. The period of their half-life does not exceed 20 minutes and in most cases lasts 1-3 minutes. Protein-peptide hormones quickly accumulate in the liver, where they are intensively degraded and inactivated by specific peptidases. This process can be observed in other tissues, as well as in the blood. Metabolites of protein-peptide hormones are apparently derived mainly in the form of free amino acids, their salts and small peptides. They are excreted in the first place with urine and bile.

Hormones often have a fairly pronounced tropism of physiological action. For example, ACTH acts on cells of the adrenal cortex, adipose tissue, nervous tissue; gonadotropins - on the cells of the gonads, the hypothalamus and a number of other structures, i.e. Organs, tissues, and target cells. Hormones of the pituitary and hypothalamus have a wide range of physiological effects on cells of different types and on various metabolic reactions in the same cells. The structure of the body according to the degree of dependence of their functions on the action of these or other hormones are divided into hormone-dependent and hormone-sensitive. If the first are completely conditioned by the presence of hormones in the process of full differentiation and functioning, the hormone-sensitive cells clearly display their phenotypic signs and without the corresponding hormone, the degree of their manifestation being modulated by it in a different range and determined by the presence of special receptors in the cell.

The interaction of hormones with the corresponding receptor proteins is reduced to non-covalent, reversible binding of hormonal and receptor molecules, resulting in the formation of specific protein-ligand complexes that can include multiple hormonal effects in the cell. If the receptor protein is absent in it, then it is resistant to the action of physiological concentrations of the hormone. Receptors are the necessary peripheral representatives of the corresponding endocrine function, which determine the initial physiological sensitivity of the reacting cell to the hormone, i.e., the possibility and intensity of reception, carrying out and realization of hormonal synthesis in the cell.

The effectiveness of hormonal regulation of cellular metabolism is determined both by the amount of the active hormone entering the target cell and by the level of receptor content in it.