SOMATOSTATIN — the hypothalamic neurohormone having ability to suppress secretion of somatotropic hormone and some other hormones of a hypophysis and peripheral closed glands, and also enzymes of digestive tract.
For the first time S. was found in extracts from hypothalamus (see) L. Krulich, etc. in 1967 it is also allocated in the cleared Brazo <R. type of Brazeau), etc. in 1973 It was established that S. represents the peptide constructed of 14 amino-acid remains in Krom two rests of cysteine are connected by a disulfide bridge:
In S.'s organism it is synthesized preferential in hypothalamic kernels, and also in other parts of the nervous system and in went. - kish. path. In the course of an embryogenesis the first cells synthesizing S. appear at first in a pancreas, a duodenum and intestines (a 8 weeks embryo), - and only on the 15th week of pre-natal development such cells appear in a hypothalamus. Early and preferential localization of S. in a pancreas of a fruit indicates its significant role in development of a digestive tract and in regulation of endocrine functions of a pancreas (see). The page contains in a type of granules of an amorphous structure and low electron-optical density in the argyrophil D-cells of type Ah located between (3 cells of the insulyarny device holding central position, and A2 cells, located on the periphery of pancreatic islands.
The page suppresses in vivo and in vitro basal and stimulated secretion of somatotropic hormone (cm) — STG — and stimulated tiro-liberiny secretion of thyritropic hormone (see). At healthy people of the inhibiting influence of somatostatin on secretion of AKTG it is not revealed while at patients with adrenal insufficiency of various genesis (see. Adrenal glands ) similar influence of S. of In vivo C. was noted does not influence basal and stimulated secretion prolactin (see), but in an experiment on culture of cells of a front share of a hypophysis the considerable inhibition by somatostatin of synthesis of prolactin these cells was revealed. The page depresses directly beta cells of the insulyarny device in the first and second phases of secretion insulin (see), surpassing in drag of synthesis of insulin even high concentration of glucose, and also on alpha cells, oppressing synthesis glucagon (see).
The page slows down secretion gastrin (see), pepsin (see), hydrochloric acid (see), secretin (see), cholecystokinin (see), the gastric inhibiting polypeptide, a neyrotenzin, the enteroglyukagona, oppresses motility of a stomach (see), intestines (see) and a gall bladder (see), has vasopressor influence on vessels of a mezenterialny zone. Assume that S. the neurotrance-mitternuyu plays a role since it is found in the terminations of nerves and in sinaptosomny sites of a cerebral cortex. The page influences the speed and completeness of absorption in intestines. At the same time it is shown that substances of food influence, in turn, S.'s secretion in a stomach, intestines and a pancreas, edge reaches a maximum in the 60th minute after meal.
The page is originally synthesized in the form of the proteinaceous predecessor — pro-somatostatin, from to-rogo it is formed as a result of hydrolysis by proteolytic enzymes. The nucleotide sequence of MRNK coding biosynthesis of pro-somatostatin is established.
For definition biol. S.'s activities use various tests: suppression under the influence of S. of secretion of STG hypophyses of rats or sheep or culture of cells of hypophyses of rats of in vitro; suppression of secretion of insulin and glucagon insular fabric, cuts or culture of cells of a pancreas of in vitro; braking under the influence of S. of increase of concentration of STG in a blood plasma of rats caused by administration of nembutal, morphine or other influences; S.'s braking increases in content of insulin and a glucagon in blood of rats after administration of arginine; decrease under the influence of S. of secretion of insulin and a glucagon a perfuziruyekhmy pancreas.
For S.'s definition in blood, urine and fabrics Takesita (T. Takeshita, 1980), Penmen (E. Penman, 1979), etc. are offered radio immunological methods (see. Radio immunological method).
At healthy people with urine hour of somatostatin is allocated 167 ± 45 pg/, S.'s concentration in blood makes 28 ± 7 ml of ml. Between S.'s maintenance in blood and urine accurate correlation is found. Cerebrospinal liquid of the person contains 35 pg, ml of somatostatin. In experiments on animals it is established that S.'s concentration in blood of a hypothalamus is 5 — 10 times higher, than in peripheral blood. At a somatostatinoma — the tumor consisting preferential of the D-cells containing S., concentration of this hormone in blood increases by 40 times (see. APUD-system ).
As a result lab. synthesis two forms of synthetic S. — cyclic with a disulfide bridge and linear (without such communication), or dihydrosomatostatin are received. Several analogs of S. are synthesized, shown that removal of the rest of a lysine in the 9th situation leads to falloff of hormonal activity of drug since the lysine-9 participates in S.'s linkng with peripheral receptors. Page was one of the first proteinaceous and peptide hormones (see) synthesized by microorganisms that was reached by means of methods genetic engineering (see).
S.'s polyfunctionality considerably complicates its use in clinic. Much more widely than perspective of use of synthetic analogs of S. with selective biol. properties and sufficient duration of action (time of half-decay of S. makes 2 — 4 min.). S.'s use at treatment of a diabetes mellitus in combination with insulin, in prevention of diabetic ketoacidosis is described; at patients with an acromegalia noted decrease in concentration of STG in blood at S. Sushchestvuyut's introduction secretions of a glucagon, these, testimonial of S.'s inhibition, a glucagonoma, gastrin — a tumor of a pancreas at the patient with a syndrome Zollinger — Ellisona (see. Zollingera — Ellisona a syndrome ), insulin — insulinomy. Consider perspective S.'s use and its derivatives at treatment of a peptic ulcer and pancreatitis, at nek-ry forms of a breast cancer, for prevention of diabetic angiopatiya, a hyperthyroidism, etc.
See also Hypothalamic neurohormones .
Bibliography: Alekseev Yu. P. Somatostatin, its physiological value and use in clinic of internal diseases, Probl. endocrinins., t. 23, No. 6, page 93, 1977; At about l e in A. M. Enterinovaya (intestinal hormonal) system, L., 1978; Physiology of endocrine system, under the editorship of V. G. Baranov, page 414, 507, L., 1979; With h and at v i and 1 1 e J. And. and. lake of Ontogeny of somatostatini in the human gastrointestinal tract, endocrine pancreas and hypothalamus, Acta endocr. (Kbh.), v. 94, p. 1, 1980; Konturek S. J. Somatostatin and gastrointestinal secretion and motility, in book: Gastrointestinal gor-mones and pathology of the digestive system, ed. by M. Grossman a. o., p. 207, 227, N. Y. — L., 1978; V a n d e r s with h u e-r e n - L o d e w e at with k x M. a. o. Somatostatin and the secretion of growth hormone induced by exogenous cyclic 3 ':5' — adenosine monophosphate in man, Acta paediat. belg., v. 29, with. 153, 1976; Was s J. A. a. o. Circulating somatostatin after food and glucose in man, Clin. Endocr., v. 12, p. 569, 1980.
Yu. A. Knyazev, G. V. Tangtsnova.