THE FEMALE SEX HORMONES

The gonads produce germ cells and sex hormones, these 2 functions are necessarily approximated (spermatogenesis and testosterone production in the testes and oogenesis and estradiol production in the ovary.)

BIOSYNTHESIS AND METABOLISM OF OVARIAN HORMONES: The estrogens are a family of hormones synthesized in a variety of tissues, 17 -bEstradiol is the primary estrogen of ovarian origin. Estrogens are formed by the aromatization of androgens in a complex process that involves 3 hydroxylation steps each of which requires O2‑ and NADPH, the aromatase enzyme is thought to include a P450 mixed –function oxidase. Estradiol is formed if the substrate of this enzyme complex is TT, where as esterone results from the aromatization of androstenedione.

Theca cells are the source of androstendione and TT, these are converted by the aromatase enzyme in granuloza cells to esterone and estradiol respectively. Progesterone is produced and secreted by the corpus luteum ,which also makes some estradiol . Significant amounts of estrogens are produced by the peripheral aromatization of androgens ,in human male the peripheral aromatization of TT to E2 accounts for 80% of the production of E2. In female adrenal androgens are important substrates ,since as much as 50% of the E2 produced in pregnancy comes from aromatization of androgenes. Finally, the conversion of androstenedione to esterone is the major source of estrogens in postmenopausal female. Aromatase activity is present in adipose cells and also in liver, skin, and other tissues, increase activity of this enz. May contribute to the “esterogenization”that characterizes such disease as cirrhosis, of liver, hyperthyroidism, aging, and obesity.

ESTROGENS AND PROGESTINS BIND TO PLASMA PROTEINS: Estrogens are bound to SHBG and progestins to CBG, SHBG binds estradiol about five times less avidly than it binds TT or DHT, while progesterone and cortisol have little affinity for this protein. In contrast prog. And cortisol bind with nearly equal affinity to CBG, which in turn has little avidity for estradiol and even less for TT, DHT, or esterone.The metabolic clearance rates of these steroids are inversely related to the affinity of their binding to SHBG ,hence esterone is cleared more rapidly than estradiol, which in turn is cleared more rapidly than TT or DHT.

The rate of secretion of ovarian steroids varies considerably during the menstrual cycle and is directly related to rate of production in the ovary. There is no storage of these compounds they are secreted when they are produced.

METABOLISM OF ESTROGENS AND PROGESTERONE: A.Estrogens: the liver converts estradiol and esterone to estriol so the E2,E1,E3 are substrates for hepatic enzymes that add glucuronide or sulfate moities then the conjugated steroids are water soluble and don’t bind to transport proteins ,so excreted in bile ,feces ,and urine. B.Progestins: It also metabolized by liver to several compounds and excreted in the urine as sodium-pregnanediol 20- glucuronide. So it is ineffective when given orally, other derivatives of 17-alpha hydoxy progesterone and 17alpha –alkyl-substituted 19-nortestosterone compounds have proge. Activity and avoid hepatic metabolism so can be used as contraceptive drugs.

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