Estrogen Progestin And Androgen Transport And Metabolism

The principal sex steroids in the female are estrogen, progestin, and androgen. Three estrogens are present in significant quantities—estradiol, estrone, and estriol. Estradiol is the most abundant and is 12 and 80 times more potent than estrone and estriol, respectively. Much of estrone is derived from peripheral conversion of either androstenedione or estradiol (see Fig 37.9). During pregnancy, large quantities of estriol are produced from dehydroepiandrosterone sulfate after 16a-hydroxylation by the fetoplacental unit (see Chapter 39). Most estrogens are bound to either albumin (~60%) with a low affinity or to sex hormone-binding globulin (SHBG) (~40%) with high affinity. Estrogens are metabolized in the liver through oxidation or conversion to glucuronides or sulfates. The metabolites are then excreted in the urine.

The most important progestin is progesterone. It is secreted in significant amounts during the luteal phase of the menstrual cycle. During pregnancy, the corpus luteum secretes progesterone throughout the first trimester, and the placenta continues progesterone production until parturition. Small amounts of 17-hydroxyprogesterone are secreted along with progesterone. Progesterone binds equally to albumin and to a plasma protein called corticos-teroid-binding protein (transcortin). Progesterone is metabolized in the liver to pregnanediol and, subsequently, excreted in the urine as a glucuronide conjugate.

Circulating androgens in the female originate from the ovaries and adrenals and from peripheral conversion. An-drostenedione and dehydroepiandrosterone (DHEA) originate from the adrenal cortex (see Chapter 34), and ovarian theca and stroma cells. Peripheral conversion from an-drostenedione provides an additional source of testosterone. Testosterone can also be converted in peripheral tissues to dihydrotestosterone (DHT) by 5a-reductase. However, the primary biologically active androgen in women is testosterone. Androgens bind primarily to SHBG and bind to albumin by about half as much. Androgens are also metabolized to water-soluble forms by oxidation, sulfation, or glucuronidation and excreted in the urine.

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