TESTOSTERONE — the male sex hormone having the greatest androgenic activity. Deyvidom is for the first time allocated in 1935 (To. David) from seed bubbles of a bull, and then A. Butenandtom, and also L. Ruzicka is synthesized.
On the chemical structure of T. is the steroid belonging to group of an androstan and represents androst-4-en-17 beta ol - Zones (see fig. to St. Androgens ).
To allocation of T. receiving in 1931 by A. Butenandt and Cherning (K. T preceded scheming) from urine of men of androsterone, to-ry as assumed, and is male sex hormone. Later it was established that the androsterone emitted with urine is formed at metabolism of testosterone and the T has considerably smaller biological activity, than.
Synthesis of T. passes the same stages, as synthesis of other androgens in an organism (see), and is under control of the luteinizing hormone (see) interacting with specific receptors dough-steronprodutsiruyushchikh of fabrics of gonads.
T. it is formed in testicles, ovaries and adrenal glands. In testicles it is produced by hl. obr. cells of Leydnga, in ovaries — cells of tekiovarialny follicles, and also in interstitial fabric of a bast layer. At the adult man 4 — 7 mg of testosterone a day, are formed of this quantity apprx. 0,5 mg — in adrenal glands. Ovaries and adrenal glands of the adult woman produce about 0,5 mg of testosterone a day.
Ground mass of T., circulating in blood, is in a type of a bio-complex with specific transport protein — testosterone-estradio of l the connecting globulin (TESG). Testosterone connected with TESG does not enter metabolic transformations. Linkng of testosterone with TESG is one of the factors determining speed its metabolic clearance (see). Metabolic transformations of T. are carried out in a liver, kidneys, intestines, lungs, skin and other bodies. The special place in metabolism of testosterone belongs to its turning into target tissues.
General orientation of exchange of T. in peripheral fabrics comes down to enzymatic recovery of D4 double bond and Z-keto-gruppy of a ring And, and also to oxidation of the 17th beta and hydroxylic group. The main metabolites which are formed as a result of these transformations are androsterone and etiocholanolone; besides, are formed epiandrosteron and 5 beta андростан-3 beta ol - 17 - it.
Androgenic activity of these metabolites is much lower, than
T. U of the person have metabolites of T. are excreted generally with urine in the form of conjugates with glucuronic and sulfuric to-tami. Being 17 ketosteroids on the structure, these metabolites can be quantitatively defined by Tsimmermann's reaction (see. 17 Ketosteroids ).
5a-reduktazny reaction is characteristic of metabolic transformation of testosterone in target tissues, as a result the cut is formed 5alfa-di-hydrotestosterone. This process is a necessary stage biol. effects of testosterone since the 5alfa-dihydroform contacts receptors of target tissues. The 5th alpha Dihydrotestosterone has bigger androgenic activity, than T., in this regard nek-ry researchers consider T. as pro-hormone.
One of ways of metabolism of T. its enzymatic aromatization in peripheral fabrics is. Extra gonadal formation of estrogen at aromatization of T. in peripheral fabrics increases products of estrogen at men normal, at women is after a menopause, and also at nek-ry patol. states.
Biol. action of T. it is most specific it is shown in target tissues where there is its selective accumulation. Receptors of T. are found in cells of seed tubules, in an epididymis, a prostate, seed bubbles, a hypothalamus, a uterus, ovarian follicles at certain stages of development.
Androgenic activity of T. in a male body it is shown in the pre-natal period when it cosecreted by testicles of a fruit provides a sexual differentiation of a hypothalamus, and also formation internal and external genitals on men's type. During puberty under the influence of T. there is a formation of generative organs and development of secondary sexual characteristics. During the reproductive period of T. stimulates certain stages of a spermatogenesis, and also maintains sexual activity of an organism.
In a female body of T. possesses specific action on processes of biosynthesis in cells of a uterus, and also influences development of ovarian follicles.
T. possesses the expressed anabolic action connected with stimulation of synthesis of protein, a cut it is shown during the formation of a phenotype of both a male, and female body. Decrease in secretion of T. in a male body at primary or secondary hypogonadism exerts impact on formation of external genitals, development of secondary sexual characteristics and a spermatogenesis. Wedge, symptomatology of a hypogonadism in many respects is defined by degree of insufficiency of development of T. and that stage of ontogenesis, on Krom this disturbance arose (see. Hypogonadism ).
Women have a hypersecretion of T. adrenal glands (an adrenogenital syndrome, the virilizing tumors of adrenal glands) or ovaries (the virilizing tumors of ovaries, a syndrome of Matte — Leventalya) leads to disturbance of generative function of ovaries, and also to virilescences (see).
Maintenance of T. reflects the level of its products in blood and it is used as diagnostic criterion. For determination of T. in blood flyuorimetrichesky methods are offered (see. Flyuorimetriya ). For the purpose of preliminary allocation of T. apply different types of a chromatography (see), including gas-liquid, a method of a double isotope tag. The greatest distribution to a lab. to practice received a radio immune method of determination of T. in blood (see. Radio immunological method), and also competitive protein binding method.
Maintenance of T. in blood healthy men of reproductive age have in limits 10 — 40 nmol/l. Level T. in blood at men is defined generally by secretion of this hormone in testicles.
Maintenance of T. in blood women have in limits 0,7 — 3 nmol/l. At the same time about a half of the general of T., circulating in blood of women, it is formed at peripheral metabolism of A4 androstendion.
For identification of functional reserves of hormonal activity of testicles use the test with introduction of a chorionic gonadotrophin (see). Differentiation of a contribution of adrenal glands and gonads in total production of T., circulating in blood, make in a wedge, conditions by means of a functional trial with dexamethasone and a chorionic gonadotrophin.
Determination of T. in urine has limited diagnostic value since allocation with urine of not metapain-zirovannogo of testosterone makes 1% of its total production.
Testosterone as drug
In clinic is used by synthetic ethers T., having the prolonged effect.
Testosteroni propionas possesses biol. action of T., but it is more slowly soaked up and is more resistant, than T. Vvodyat intramusculary in the form of oil solution. The highest single dose makes 50 mg, daily — 100 mg.
Testosteroni oenanthas is a part of drug Testoenatum (Testoenatum), to-ry testosterone-enanthate contains apprx. 20% testosterone-propionate and 80%. In this combined drug the fast-soaking-up testosterone-propionate provides bystry development of effect, and testosterone-enanthate — the prolonged action.
Methyltestosteronum on activity is 3 — 4 times weaker testosterone-propionate, entered intramusculary; apply sublingual.
To men drugs T. appoint at a wedge, the forms of testicular insufficiency, diseases connected with disturbance of a sexual differentiation, disturbances of sexual function. Besides, drugs T. use for treatment of climacteric frustration, and also an age prostatauxe. At a prostate cancer they are contraindicated.
Women have drugs T. apply to treatment of climacteric frustration, dysfunctional uterine bleedings, and also in complex therapy of a breast cancer. Hormonal therapy estrogenzavi-simy a form of a breast cancer is directed to suppression of oestrogenic activity and blocking of development of gonadotrophins, it should be seen off during all life of the patient. Introduction of large numbers of T. (350 — 400 mg a month) can cause disturbances of a water salt metabolism, and also a masculinization of a female body.
Bibliography: Biochemistry of hormones and hormonal regulation, under the editorship of N. A. Yudaye-va, page 246, M., 1976; Vartane-t about in B. A. and Demchenko A. N., the Climax at men, page 177, Kiev, 1965; The Guide to clinical endocrinology, under the editorship of V. G. Baranov, L., 1976; Starkova H. T. Fundamentals of clinical andrology, M., 1973; Fizer Li Fizer M. Steroids, the lane with English, page 520, M., 1964; Physiology of endocrine system, under the editorship of V. G. Baranov, etc., page 341, L., 1979; David K. tlber das Testosteron, das kristallisierte mannliche Hormon aus Stierentestes, Acta brev * neerl., Physiol., v. 5, p. 85, 108, 1935; Testosterone, ed. by J. Tamm, Stuttgart, 1968.
V. S. Zelenetskaya.