Androstenedione, adrenal production

Aminoglutethimide [ah me no glue TETH i mide] is useful in second line therapy for the treatment of metastatic breast cancer. It inhibits the adrenal synthesis of pregnenolone from cholesterol, and the extra-adrenal aromatase reaction responsible for the synthesis of estrogen from androstenedione. Aminoglutethimide is administered orally, and is metabolized by the hepatic cytochrome P-450 system to inactive products. Because of its ability to induce this system, its own metabolism is accelerated, and interactions that increase the metabolism of dexamethasone (see p. 275), theophylline (see p. 220) and digoxin (see p. 158) can occur. Aminoglutethimide causes transient CNS depression and a maculopapular rash. 

Overall, other adrenal androgens also show a progressive decrease in urinary excretion in both men and women. Thus, the mean 17-ketosteroid urine levels of elderly people are about 50% of those in young adults. This is primarily secondary to decreased dehydroepiandrosterone (DHEA) and androsterone production. In men, about one-third of the daily 17-ketosteroids are of testicular origen, the remainder being mainly from the adrenals. Androstenedione is a prehormone for testosterone. 

The liver is the most important area for (he production of cholesterol and bile acids. The ovaries are the most important sources of estrogen and progesterone (progesterone is produced in the corpus luteum of the ovary). The testes are the major site of androgen production, testosterone especially. The adrenal cortex produces the mineralocorticoids and glucocorticoids, and the androgens dehydroepiandrosterone and androstenedione. 

In the normal, nonpregnant woman, estradiol is produced at the rate of 100 to 300pg/day. The production of estrone ranges from 100 to 200pg/day. Diurnal variation of blood estrone concentrations occurs in postmenopausal women, presumably reflecting the variation in the androstenedione precursor that originates in the adrenal glands. However, no such diurnal rhythms have been demonstrated for estradiol. 

The bulk of the urinary 17-KSs consists of andro-sterone, epiandrosterone, etiocholanolone, DHEA, 11-keto-and lip-hydroxyandrosterone, and 11-keto- and 11(3-hydroxyetiocholanolone. DHEA and 11-oxygenated 17-KSs are produced only by the adrenal glands, whereas the others also arise from precursors (androstenedione and testosterone) elaborated by the gonads. Thus the main purpose of measuring these steroid metabolites is to assess adrenal androgen production. 

Norethynodrel, I7-a-ethinyl-17p-hj roxy-5(10)-estrene-3-one, increases eidrenal wei ts in intact female rats59. plasma and adrenal B levels decrease at the time of day dien values are normally highest. Clomiphene increases output of 17-oxysteroids in a patient with galactorrhea Cyano-trimethylandrostenolone, 2a-cyano-J4-, k, 17a-trimethyl-17p -OH- 5-androstene- 3-one, causes adrenal hypertrophy, a fall in adrenal venous 3 of male rats and inhibition of 3P-hydroxysteroid dehydrogenase l. Norethandrolone, 170(-ethyl-17P-0H- -norandrostene-3-one, stimulates the production of B by adrenals of castrated rats and increases pituitary ACTH content . This androgen partially reverses the E induced suppression of B production but not of the adrenal response to stresses. Testosterone, androstenedione, EHEA, estrone and estradiol has no effect on conversion of B to 18-OH B and Aldo by sheep adrenal mitochondria . 

Testosterone and oestradiol are known as the sex steroid hormones. Testosterone is the principal androgen and is synthesized by the testes in the male. Oestradiol. which is secreted by the ovaries, varies w idely in concentration in plasma throughout the female menstrual cycle. Steroids with oestradiol-like action arecalledoestrogens. Progesterone is a product ofthe ovary and is secreted when a corpus lutcum forms after ovulation. Normal female plasma also contains testosterone, about half of which comes from the ovary and half from peripheral conversion of androstenedione and dehydroepiandrosterone (DHA) sulphate which are secreted by the adrenal cortex. Some oestradiol is present in low concentration in normal male plasma. 

The past decade has shown that hydrocarbon desaturation is not uncommon but, except in cases such as the biosynthesis of ergosterol, it generally accounts for a minor proportion of the metabolic products. The earliest reported example of P450-mediated hydrocarbon desaturation appears to be the conversion of lindane (1,2,3,4,5,6-hexachloro-cyclohexane) to 1,2,3,4,5,6-hexachlorocyclohex-ene, but the known hydrocarbon desaturation reactions now include the A -desaturation of androstenedione and deoxycorticosterone by adrenal mitochondria, the oxidation of dihydronaphthalene to naphthalene and 7,8-dihydrobenzo[a] pyrene to benzo[a]pyrene the conversion of warfarin to dehydrowarfarin ", the desaturation of lovostatin and simvastatin to the 6-exo-methylene... 

Estrogens are biosynthesized in the maturing dominant foiiicle and in the corpus luteum in premenopausal women. During pregnancy, the placenta becomes the primary location of estrogen biosynthesis (5,6). Approximately 50% of estrone production occurs in the ovaries. The remaining estrone is biosynthesized from estradiol as well as from the conversion of estrone sulfate to estrone in the adrenal gland and the aromatization of androstenedione. In contrast to premenopausal women, in whom the natural estrone to estradiol ratio is 1 2, postmenopausal women have an estrone to estradiol ratio of 2 1, which reflects the loss of ovarian function. 

These are a group of C-19 steroids which influence the male secondary sex characteristics. They are made by the testes, adrenals and to a lesser extent by the ovaries. The testes secrete testosterone while the main adrenal androgens are dehydro-epiandrosterone and androstenedione. Urinary 17-oxosteroid estimations give an indication of androgen production. 

Hormones with androgenic activity are produced not only by the testes, but by the adrenal cortex as well, e.g. androstenedione and 11-hydroxyandroslenedione. Under certain conditions, such as tumor of the adrenal cortex, the androgen production may rise greatly in women this causes the pathologic condition known as virilism. 

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