PROGESTERONE (pregn-4-en-3,20-dion) — the steroid hormone synthesized by a yellow body of an ovary, cortical substance (bark) of adrenal glands, seed bubbles and a placenta; drugs of progesterone I of some of its synthetic analogs are used as pharmaceuticals. Determination of content of P. in blood or determination of content of its main metabolite — pregnandiol in urine has great diagnostic value, especially at not incubation of pregnancy and infertility.
The item belongs to With 21 - to steroids also has the following chemical structure:
The item was selected in 1928. G. W. Corner and Allen (W. The m of Allen) from a yellow body of ovaries of a pig, and in 1934 is synthesized by A. Butenandt.
P.'s biosynthesis happens in ovaries (see) — lyuteiuovykh cells yellow body (see), to a placenta (see) through the general for all C21 steroids of a stage also proceed: cholesterol —> 20, 22-dioxycholesterol —> pregnenolon —> progesterone. P.'s education in ovaries out of pregnancies (see) it is regulated luteinizing hormone (see), and at pregnancy — chorionic gonadotrophin (see). The maximum daily products of P. in a lyuteinovy phase menstrual cycle (see) makes 10 — 20 mg, and during pregnancy increases by 9 — 10 times. Speed of metabolic clearance (see) P. makes 2400 l a day. P.'s metabolism proceeds preferential in a liver with formation of a number of biologically inactive derivatives, pregnandiol is basic of which. It is established that 50 — 60% of P. entered into an organism are excreted with urine in the form of metabolites.
Biol, P.'s effect is carried out on the general for all steroid hormones (see) the mechanism. The item interacts with specific cytoplasmatic proteinaceous receptors, the formed complex is transferred to a kernel of a cell and activates certain structures chromatin (see). Stimulation of synthesis of specific proteins and change of a functional condition of target organs results.
The item participates in regulation of cyclic transformation of an endometria. Under the influence of P. there is a secretory transformation of an endometria in a lyuteinovy phase of a menstrual cycle, and also functional changes in uterine tubes (see), vagina (see) and an epithelium of mammary glands (see. Mammary gland ). One of the main fiziol, functions P. is braking of sokratitelny function of a myometrium, especially during pregnancy. Decrease in secretion of P. a yellow body (out of pregnancy) results in insufficiency of a lyuteinovy phase of a menstrual cycle and to defective secretory transformation of an endometria. It is established that F2alfa prostaglandin oppresses P.'s education in granular cells of a follicle, and prostaglandin E 2 stimulates formation of the Item in them.
P.'s maintenance in blood in the first phase of a menstrual cycle — a follikulinovy phase — makes 0,4 — 0,8 ng/ml, and in a lyuteinovy phase — from 3 to 30 ng/ml (depending on day of a cycle). In the period of the maximum activity of a yellow body (18 — the 23rd days of a normal 28-day menstrual cycle) P.'s maintenance in blood lower than 7 ng/ml testify to hormonal insufficiency of a yellow body. The relative hyperestrogenemia results that is followed by development of such hormonal and dependent diseases as polyposes of an endometria, endometriosis (see), hysteromyoma (see), dishormonal hyperplasia of mammary glands, etc. Along with it at disturbance of maturing of a follicle anovulation can be observed (see. Anovulatory cycle ), owing to what the yellow body is not formed and P.'s synthesis does not happen that causes emergence of a monophase cycle with development of hyperplastic processes of various degree of manifestation in target organs.
At normally current pregnancy P.'s maintenance in blood increases from 15 to 25 ng/ml in the first trimester and by the end of pregnancy can reach 200 ng/ml. During the first trimester of pregnancy decrease in education of P. a yellow body can lead to abortion — an abortion.
P.'s definition is based on the principle of the sating analysis using radio immunological methods or competitive binding by proteins.
Drugs of progesterone
Drugs of progesterone appoint in to lay down. the purposes at various diseases which genesis is connected with its deficit. For a wedge. uses use P., pregnenoldione kapronat, acetoxyprogesterone and some other synthetic analogs of P., napr, Pregninum (see), and others progestins (see).
Progesteronum represents white crystal powder, low solubility in water, it is slightly better soluble in vegetable oils and it is good — in alcohol.
At dysfunctional uterine bleedings (see) as a result of anovulation or a defective lyuteinovy phase P. it is appointed intramusculary with 16 — the 18th day of a menstrual cycle within 6 — 8 days on 1 ml in the form of 1% of oil solution. The similar scheme of introduction of P. can be applied at treatment of endometriosis, dishormonal diseases of mammary glands and to prevention a polypose and a hyperplasia of an endometria. However for treatment of these patol, states preference is given to synthetic progestins which are 10 — 15 times more effective.
Items produce in the form of 1% and 2,5% of oil solutions in ampoules 1 ml.
Pregnenoldione kapronat is drug P. of the prolonged action. Differs from P. in presence of the rest kapron to - you at C17 - atom and in comparison with P. has slower effect that often complicates its use at therapy of dysfunctional uterine bleedings and some other ginekol. the diseases demanding acute management. Depending on the entered dose the effect of pregnenoldione of a kapronat lasts of 7 days to 2 weeks. The broadest use in a wedge, practice of pregnenoldione kapronat received at cancer therapy of a body of the womb; in this case it is entered on 500 mg intramusculary daily, on a course 8 — 10 g. At dysfunctional uterine bleedings on 16 — 1 — 2 ml of 12,5% of solution of pregnenoldione of a kapronat once enter the 18th day of a menstrual cycle. Produce pregnenoldione kapronat in the form of 6,5%, 12,5% and 25% of oil solutions in ampoules 1 ml.
Drug P. for intake is acetoxyprogesterone, close to pregnenoldione to a kapronat on properties and indications to use. It is appointed in the form of tablets on 0,005 g under language. These tablets do not collapse in an oral cavity and therefore have long resorptive effect.
Store drugs P. and its synthetic analogs in the place protected from light; joint venture. B.
As a rule, drugs P. have no side effect on an organism of the woman, however it is necessary to reckon with their certain androgenic activity that can have an adverse effect on fetation, causing in it disturbances in formation of urinogenital system, including ovaries. The item is an antagonist Aldosteronum (see) therefore sharp cancellation of drugs P. can cause the phenomena in some cases hyper aldosteronism (see).
Bibliography: Biochemistry of hormones and hormonal regulation, under the editorship of N, A. Yudaye-va, page 171, etc., M., 1976; Gynecologic endocrinology, under the editorship of. K. N. Zhma-kina, page 26, etc., M., 1980; Mashkovsky M. D. Pharmaceuticals, p.1, page 599, M., 1977; Rosen V. B. Fundamentals of endocrinology, page 41, etc., M., 1979; Rosen V. B. and Smirnov A. I. Receptors and steroid hormones, page 27, etc., M., 1981; Regulation of human fertility, ed. by E. Diszfalusy, Copenhagen, 1977.
I. A. Manuylova, H. D. Fanchenko; D.N. Samoylov (pharm.).