HYPOTHALAMIC NEUROHORMONES (Latin. hypothalamicus; neurohormones) — group of the hormones of the peptide nature cosecreted by a hypothalamus in portal vessels of an adenohypophysis and stimulating or oppressing release of triple hormones of a hypophysis. Of N participate in regulation of all vital biol, functions (growth and development of an organism, activity of hemadens) and, besides, provide interaction of the highest departments of c. N of page and endocrine system. Of N is designated also rileasing-factors or rileasing-hormones (to release English release). For designation of certain representatives of this group of hormones use the name «rileasing-factor» more often (e.g., G. the N stimulating release of thyritropic hormone of a hypophysis is called a thyrotropin-rileasing-factor). In 1974 new terms for designation of these hormones are offered: «liberina» — for stimulators of release and «statines» — for inhibitors of release of hypophyseal hormones.
G.'s classification N is based on the so-called unitary concept, edges is that one G. the N stimulates (or oppresses) release of one corresponding hormone of a hypophysis. The evidence of existence in a hypothalamus of seven stimulators and three inhibitors of secretory function of a hypophysis is obtained: AKTG-rileasing-faktor (KRF) — kortikoliberin; the thyrotropin-rileasing-factor (TR) — tiroliberin; a rileasing-factor of luteinizing hormone (LRF) — lyuliberin; a rileasing-factor of follicle-stimulating hormone (FSG-RF) — folliberin; a Somatotropinum-rileasing-factor (TsRF) — somatoliberin; the prolactin-rileasing-factor (PR) — prolaktoliberin; a rileasing-factor of melanocyte stimulating hormone (MRF) — melanoliberin; the prolactin-the inhibiting factor (PIF) — pro-lactostatine; the inhibiting factor of melanocyte stimulating hormone (MYTH) — melanostatin; the Somatotropinum-the inhibiting factor (SIF) — somatostatin.
The researches of the chemical nature of G. of N begun more than 20 years ago led to clarification of structure only of three hormones of this group: TRF, LRF and CIF (somatostatin). The specified connections received in the synthetic way represent the oligopeptida consisting of 3, 10 and 14 amino acids:
Structures of TRF and LRF have common features: on the N-end of these peptides there is a rest pyroglutaminic to - you, and on the C-end amide group. Unlike TRF and LRF, N-and C-endgroups of somatostatin are free. Other G. of N are received only in partially cleared look therefore their chemical nature is completely not established. Difficulties of allocation and G.'s studying of N are connected with is insignificant the small (nanogram) content of these substances in a hypothalamus and insufficient specificity of methods of definition biol, activities of some of them. Usually about G.'s activity of N judge by quantity of the hypophyseal hormone defined radioimmunologichesk which is released on Wednesday or blood in response to G.'s introduction in N of in vitro or in vivo. Supersensitive radioimmunol. systems are used for determination of content of G. of N in blood and urine.
Establishment of the peptide nature of G. of N helps clarification of the mechanism of their education and disintegration. Concerning TRF it is known that this tripeptide is synthesized in a hypothalamus in the neribosomalny way from amino-acid predecessors in the presence of ATP and the specific SH enzyme named by TRF-sintetaza or system of enzymes. Similar data are obtained also concerning formation of LRF, SRF and PRF. However questions of the enzymatic mechanism of education of G. of N and his regulation are a little studied and need further researches. It is supposed that nerve terminations («synaptosomes») in which also biogenic amines stimulating release of the specified hormones from neurosecretory cells in capillaries of portal system are found can serve as the place of formation of these hormones. Biogenic amines along with hormones of the peripheral closed glands operating on a hypothalamus by the principle of a feed-back consider as regulators of secretion and G.'s synthesis of N. A little still it is known of the main ways by means of which N are inactivated and brought by G. from an organism. Bystry loss of activity of TRF under the influence of plasma of the person and some animals is connected by hl. obr. with enzymatic eliminating of C-trailer amide group. (Depending on features of their structure) it is possible to carry to enzymes of metabolism of G. of N both classical ekzo-and endopeptidases, and proteolytic enzymes of special specificity (e.g., the piroglutamilpeptidaza, edges are chipped off by the N-trailer rest pyroglutaminic to - you in TRF and LRF, inactivating them).
Of N, as a rule, vidonespetsifichna. Under the influence of these hormones (in vivo) the person and various animals have a bystry and significant increase in concentration of the corresponding hormones in plasma. So, after intravenous administration of nanogram doses of TRF and LRF to the rats who are previously processed by estrogen and progesterone, the stimulating effect is found in 3 min., in 5 — 10 min. reaches a maximum (increase by 3 — 20 times) and in 40 — 60 min. disappears. In various in vitro G. systems of N are active at concentration 10 - 6 — 10 - 8 asking. Effect of these hormones is directed directly to adenogipofizarny cells, and their intaktnost — a necessary condition for manifestation of hormonal effect; stimulation of release of hormones does not come from the isolated cellular granules and homogenate of a hypophysis. The researches conducted with synthetic drugs G. of N showed that TRF causes increase in release not only Thyrotropinum, but also prolactin, LRF — release of luteinizing and follicle-stimulating hormones, CIF oppresses secretion of Somatotropinum and Thyrotropinum and, besides, has ability to inhibit release of hormones of a pancreas — insulin and a glucagon. These data contradict the unitary concept. It is possible that the multiple nature of action of G. of N is a consequence of a certain functional condition of adenogipofizarny receptors, a cut in turn depends from experimental or patol, conditions (especially on concentration of the hormones circulating in blood). Apparently, functional condition of receptors defines the answer of a hypophysis to this or that incentive.
G.'s influence is established to N not only on secretion of hypophyseal hormones, but also on their biosynthesis. It is supposed that G. of N selectively interact with elements of the receptor localized in plasma membranes of adenogipofizarny cells. Such interaction is resulted by conformational changes in a gormono-receptor complex, its reorganization or dissociation leading further to change of activity of some fermental systems of a membrane, including and adenyl cyclase. Activation of the specified fermental systems can cause dissociation of the complex of ions Ca connected with membranes 2+ — ATP that leads to release of ions of Ca 2+ and substrate of adenyl cyclase — ATP. The formed cyclic AMF (tsAMF) serves as the intermediary in further transfer of the hormonal signal sent most likely at the same time on change of release and synthesis of the corresponding hormone of a hypophysis. tsAMF works through activation of the tsAMF-dependent protein kinases which are carrying out phosphorylation of various structures. So, phosphorylation of proteins of ribosomes can lead to acceleration of synthesis of the cosecreted hormone. Phosphorylation of some structures of membranes of secretory granules and plasma membranes which immediately join in secretory process is followed by merge of the specified membranes and release of secretory protein by means of an exocytosis. It is possible to assume that as a result of the modification of cellular membranes happening under the influence of G. of N intracellular ion concentration of calcium or due to strengthening of their exogenous penetration into a cell, or due to release of this ion from its membrane complexes increases. The crucial role in start of secretory processes is assigned to calcium ions. Apparently, the mechanism of inhibitory effect of somatostatin on secretion of some peptide hormones in two various endocrine structures (a hypophysis and a pancreas) includes elimination from secretory process of a calcium ion by means of binding it with tetradecapeptide or owing to existence of antagonism between a calcium ion and this peptide.
Change of secretion of G. of N influences biosynthesis and allocation by a front share of a hypophysis of the corresponding triple hormones. It finds the wedge, expression in development of a number of diseases — acromegalias (see), Itsenko's diseases — Cushing (see. Itsenko — Cushing a disease ), a diffusion toxic craw (see. Craw diffusion toxic ), pituitary cachexia (see), hypothyroidism (see), etc.
Researches biol, and pharmakol, properties G. of N showed that these hormones are powerful and non-toxic stimulators of release of adenogipofizarny hormones. Drugs TRF and LRF are applied generally as means to assessment of a functional condition of a hypophysis, and also for the purpose of differential diagnosis: for clarification of localization of disturbances at the level of a hypophysis or a hypothalamus. Besides, determination of dynamics of secretion of hypophyseal hormones under the influence of G. the N allows to receive additional characteristics of functions of peripheral closed glands. Efficiency of use of G. of N in quality to lay down. means it is not finalized. Side effect of N is not revealed.
Special attention is paid to searches of synthetic analogs of LRF which are competitive inhibitors of this G. of N. It is supposed that by means of these connections there will be possible a suppression of an ovulation at the person and by that control of birth rate.
Bibliography: Yudayev N. A. iyevtikhi-N and 3. T. Modern ideas of hypothalamic rileasing-factors, in book: Sovr. vopr, endokrinol., under the editorship of N. A. Yudayev, century 4, page 8, M., 1972, bibliogr.; P about 1 k e of s K. and. lake of Chemistry and biosynthesis of the hypothalamic releasing and inhibiting neurohormones, Angew. Chemie, v. 12, p. 255, 1974; S with h a 1 1 at A. V., Arimura A. KastinK. J. Hypothalamic regulatory hormones, Science, v. 179, p. 341, 1973, bibliogr.; V a 1 e W. a.o. Effects of somatostatin on the secretion of thyrotropin and prolactin, Endocrinology, v. 95, p. 968, 1974, bibliogr.
3. F. Utesheva.