Health Information

Cytochrome P450 forms play a major role in estrogen synthesis. During pregnancy, a unique interaction among cytochrome P450 forms in different organs is needed in order to synthesize the large quantities that are required. Hormone production increases dramatically during pregnancy and, at term, the pregnant woman produces 15-20mg of estradiol, 50-100 mg of estriol, and approximately 250 mg of progesterone per 24-h period. The amount of estrogen synthesized during pregnancy far exceeds the amount synthesized by nonpregnant women. For example, the pregnant woman at the end of gestation produces 1000 times more estrogen than premenopausal women per day.

The corpus luteum of the ovary is the major site for estrogen production in the first few weeks of pregnancy, but at approximately 4 weeks of gestation, the placenta begins synthesizing and secreting progestrone and estrogens. After 8 weeks of gestation, the placenta becomes the dominant source for the synthesis of progestrone. An interesting difference between the hydroxylating systems in the placenta and the ovary is that the human placenta lacks the cytochrome P450 (CYP17) that catalyzes both the 17 alpha hydroxylation reactions and the cleavage of the C17-C20 bond. Thus the placenta cannot synthesize estrogens from cholestrol. The placenta catalyzes the side chain cleavage reaction to form pregnenolone from cholesterol and oxidizes pregnenolone to progesterone but releases this hormone into the maternal circulation. How then does the placenta produce estrogen if it cannot synthesize DHEA or androstenedione from progesterone? This is accomplished in the fetal adrenal gland, a highly active steriodogenic organ during fetal life, which catalyzes the synthesis of DHEA from cholesterol and releases it into the fetal circulation. A large proportion of fetal DHEA is metabolized by the fetal adrenal gland and liver to 16 alpha hydroxy DHEA, which is converted by CYP19 in the placenta to the estrogen estriol. This is an elegant demonstration of the cooperativity of the cytochrome P450 mediated hydroxylating systems in the fetal and maternal organ systems leading to the progressive formation of estrogens during the gestational development of the human fetus.