ESTROGEN (Greek oistros violent desire, passion + gennao to create, make; a synonym oestrogenic hormones) — group of female sex hormones. AA. are steroid hormones (see), in medical practice E. and their synthetic analogs are used as pharmaceuticals.
The term «estrogen» was entered by E. V. Allen and E. Doyzi, to-rye for the first time in 1923 found oestrogenic activity in acellular extracts of ovaries (see). Among natural estrogen prevail estrone (see), oestradiol (see) and estriol (see), physiological value, ways of education and removal to-rykh are studied fullestly, and also equilenin (it biol. activity makes V25 of biological activity of estrone) and an ekvi-lean (1/20 biological activities of estrone). On a chemical structure natural E. at the person and the majority of animal species are derivatives of estrone, C18 steroids (see Steroids) with an aromatic ring
And, phenolic hydroxylic group at the 3rd carbon atom (C3) and ketogroup or hydroxylic group at the 17th carbon atom. Along with C18 steroids oestrogenic activity also nek-ry nonsteroid connections possess. So, the highly active synthetic nonsteroid estrogen used as pharmaceuticals (see Estrogen synthetic nonsteroid) concerns to stilbene group (mezestrol, hexestrol) or is derivatives of a trife-nilalanin. Oestrogenic activity of extracts from a number of plants is caused by presence at them of flavin connections (see
Flavonoids). Features of structure and spatial configuration of molecules of these nonsteroid connections provide their high affinity to specific cellular oestrogenic receptors and define their hormonal activity.
Development of ideas of features of secretion E. considerably depended on accuracy and sensitivity of methods of definition of activity and concentration E. in biological material. In 1923. By Allen and E. Doyzi it was offered biol. the test for measurement of oestrogenic activity based that the estrogen entered to the castrated rats or mice causes changes of a mucous membrane of a vagina, characteristic of an estrus (spout), to-rye can be controlled easily at microscopic examination of vulval smears. More exact quantitative definition of estrogen was reached by means of chemical methods. In practice the colorimetric method (see Colorimetry) separate definition of estrone, oestradiol and estriol in urine at the person offered by Brown was widely adopted (J. Century of Brown) in 1955. The method consisted in consecutive alternation of acid hydrolysis of conjugates of estrogen, extractions by ether, methylations of estrogen, divisions of the received methyl ethers of estrogen by method of column chromatography (see), carrying out staining reaction and in the subsequent a range ofo that meter of AI (see) the painted reaction products. Despite complexity and labor input of a method of Brown, with his help patterns of excretion E were studied. at the person is normal also at pathology. Implementation in practice highly sensitive r adio to an imm of a nolo-gichesky method (see) allowed to obtain information on dynamics of maintenance E. in blood also led to formation of ideas of patterns of functioning of pituitary and ovarian system.
Biosynthesis E. as biochemical process represents the aromatization of C19 steroids (see. Organic compounds) catalyzed by a complex of the enzymes localized in microsomes.
Direct predecessors E. are D4-androsten-dion (see Corticosteroids) and testosterone (see).
Women of childbearing age have a ground mass there is E. it is synthesized in the ovary containing the ripening follicle or a yellow body (see. Menstrual cycle). Synthesis E. in an ovarian follicle is defined by interaction of two steroidprodu-
tsiruyushchy structures — - a granular
layer and a tekakletok of a follicle, at the same time in tekakletka under the regulating influence of luteinizing hormone (see) synthesis of C19 steroids — androgens is carried out (see), to-rye move to cells of a granular layer where there is a process of their enzymatic aromatization and turning into E. under control of follicle-stimulating hormone (see). Synthesis E. in the ripening secondary follicle (a graafovy bubble) is one of the major factors defining function of pituitary and ovarian system since strengthening E. in blood in a growth phase of a follicle causes preovulyatorny emission of luteinizing and follicle-stimulating hormones, to-rye are necessary for completion of process of maturing of a secondary follicle and an ovulation.
Education E. in an ovary throughout a menstrual cycle dynamics of their concentration reflects in blood, and also their excretion with urine. In the first 7 — 10 days of a menstrual cycle excretion E. with urine it is low and makes less than 5 mkg a day. From the 11th day of a cycle it increases, after an ovulation excretion E. decreases and again raises in a phase of a yellow body. In an early stage of a phase of proliferation of a menstrual cycle concentration E. is in blood on a fixed level (apprx. 50 — 70 pkg/ml). In process of maturing of a follicle education E. progressively increases, and concentration them in blood reaches the highest value (apprx. 250 pkg/ml) during the period preceding peak of formation of luteinizing hormone and an ovulation (so-called preovulatory peak of estrogen) and then sharply decreases. Second rise of education E. is defined by the beginning of functioning of a yellow body and it is characteristic of a phase of a yellow body (a lyuteinovy phase) of a menstrual cycle. Regression of a yellow body is followed by decrease in synthesis E. ovaries; maximum decrease in synthesis E. it is noted in 2 — 3 days prior to periods. At pregnancy education E. considerably the fruit — a placenta increases due to functioning of system. Men have approximately V3 of total quantity E. it is formed in seed bubbles (see).
Biosynthesis E. by aromatization of C19 steroids occurs not only in steroid producing hemadens (see), but also in many body tissues (fatty tissue, muscles, a liver, kidneys, etc.). Extra gonadal education E. is the basic at men, at the women who are in a postmenopause (see the Menopause), and at the women who underwent castration (see).
In blood E. generally are in a type of complexes with the transport proteins connecting steroid sex hormones (see). Formation of such complexes serves one of factors of regulation biol. activity and intensity of exchange of estrogen.
Main direction of metabolism E. the hydroxylation of a steroid kernel of their molecule in various provisions is (C2, C4, C6, with, s115 s14, s16, s16, C18), at the same time in the majority of metabolites the aromatic structure of a ring of A. U of the person most intensively remains there is a hydroxylation at the 16th carbon atom (C16) therefore 16 estriol — quantitatively prevailing metabolite E are formed. On an orientation of metabolism E. a number of factors influences. So, intensity S1b-gidroksilirovaniya increases at increase in body weight, dysfunction of a liver, decrease in concentration of thyroid hormones in blood (see. Thyroid gland). The hydroxylation of estrogen in the 2nd situation leads to formation of the metabolites which received the name catechol-estrogen since the structure of a ring And their molecule is similar to dioksi-benzene ring of catecholamines (see). This feature of structure-tekholestrogenov is of a certain interest to understanding of mechanisms of the modulating influence E. on function gipotalamo-gipofi-zarnoy systems (see). Metabolism E. occurs in target organs, kidneys, skin, erythrocytes, etc., however the central role in this process belongs to a liver. AA., circulating in a liver, meta Bol iziruyut-sya in it and with bile get in went. - kish. path, at the same time part E. it is soaked up back in blood, being exposed to reactivation. In a liver water-soluble conjugates E are formed. and their metabolites with glucuronic and sulfuric to-tami. The Kishechnopechenochny cycle and processes of activation — an inactivation E. are the mechanisms regulating exchange E. and their removal from an organism. Disturbance of these mechanisms explains emergence of a giperestrogeniya in the men sick with cirrhosis. AA. and their metabolites are excreted with urine and a stake.
Fiziol. effect E. decides by their interaction on receptors of target cells. Receptors of estro-genkompetentny cells have unequal affinity to various natural and synthetic E. So, binding an estrabottom of l and above, than hexestrol (Hexoestrolum), estrone, estriol (in decreasing order) that corresponds biol. activities listed E. concerning target cells. However fiziol. ef
fekt E. and their drugs administered in an organism depends as well on ways of transformation of these connections. Reception E. is under the difficult regulating influence of sex hormones and gonadotropic hormones (see) that defines change of sensitivity of estrogenkompetent-ny cells and structures at various physiological states.
Basic biol. action consists in their influence on formation and functioning of female generative organs (see. Urinogenital system). AA. cause increase in a uterus due to growth of a stroma of a myometrium and an endometria, under the influence of E. there is vascularization of an endometria and growth of its glands, i.e. a phase of proliferation of a uterine cycle (see the Uterus). Throughout a menstrual cycle under the influence of the changing level of secretion E. are carried out cyclic morfol. changes of a mucous membrane of a uterus and an epithelium of a vagina (see), growth of a vagina is stimulated, reaction of the environment of its contents is controlled. Nek-ry key stages of an ovarian cycle are in an ovary under control E., to-rye differentially influence sensitivity of cells of a granular layer and a tekakletok to luteinizing and follicle-stimulating hormones. Cyclic nature of secretion E. throughout a menstrual cycle is defined by the cyclic nature of emission in a blood stream of gonadotropic hormones. AA. participate in formation of secondary sexual characteristics, exert the modulating impact on various structures of a hypothalamus (see) that, in particular, finds expression in formation of a specific sexual behavior at females. An important role is played E. in regulation of function of mammary glands (see. Mammary gland). AA. influence also many functions of an organism: a lipometabolism, a metabolism in a bone tissue and in skin, on a condition of system of mononuclear phagocytes (see).
The general indications to therapy by drugs E. (see Hormonal therapy) at women clinical signs of insufficiency of production of estrogen at a hypo-ovaria serve, in a climacteric (see), and also after castration. Replacement therapy by drugs E. at these states carry out for the purpose of stimulation of development of a uterus and secondary female sexual characters (at their underdevelopment), mitigation of manifestations of climacteric and postkastratsionny frustration. AA. enter at weakness of patrimonial activity and at postmature pregnancy for sensitization of a uterus to oksitoti-chesky substances.
Contraindications to use E. at women existence of malignant and benign tumors of generative organs, a mastopathy, an endometritis, tendency to uterine bleedings serve in the medical purposes. The exception makes a breast cancer at women in a postmenopause, at Krom as an additional method of treatment apply an estrogenoterapiya is long also in high doses for the purpose of oppression of the increased formation of follicle-stimulating hormone.
At women at overdose or prolonged treatment E. uterine bleedings, increase in body weight owing to a delay of sodium and water in an organism can be observed (see the Water salt metabolism).
At men the estrogenoterapiya is carried out at a prostate cancer. At the same time emergence of a gynecomastia (see) and signs of feminization is possible (see). Synthetic E. can exert toxic impact on a liver and kidneys.
Bibliography: Rosen V. B. Fundamentals of endocrinology, M., 1984; F and z e r JI. and F and z e r M. Steroids, the lane with English, page 462, M., 1964; Physiology of endocrine system, under the editorship of V. G. Baranov, page 356, JI •, 1979. V. S. Zelenetskaya.