AROMATASE AND ESTROGEN 2-HYDROXYLASE ACTIVITIES OF HUMAN PLACENTAL MICROSOMES IN PREGNANCY-INDUCED HYPERTENSION

2-Hydroxylation is one of the major metabolic pathways of estrogens an d is believed to be catalyzed by a form of cytochrome P450. Recently i t has been reported that estrogen 2-hydroxylase activity in human plac enta is catalyzed by aromatase. Some investigators suggested the effec t of catechol estrogen on human placental steroidogenesis which may be related to pregnancy-induced hypertension (PIH) through the inhibitio n of catechol-O-methyltransferase (COMT) activity. In order to better understand the interrelationship between placental aromatase and estro gen 2-hydroxylase activities in PIH patients, both activities were eva luated in the PIH placentas. Human placental microsomes obtained from PIH patients were incubated with [1 beta-H-3]androstenedione or [2-H-3 ]estradiol in the presence of NADPH. Aromatase and estrogen 2-hydroxyl ase activities were assessed by the tritium water method. The immunosu ppression patterns of both activities due to monoclonal anti-aromatase cytochrome P450 antibody (MAb3-2C2) were studied. Estrogen 2-hydroxyl ase activity was significantly higher in PIH placentas (4.7 +/- 0.9 pm ol/min/mg protein, n=7) than in normal placentas (3.0 +/- 0.7 pmol/min /mg protein, n=7). When the PIH placental microsomes were subjected to immunosuppression by 1 to 100 mu g IgG of MAb3-2C2, estrogen 2-hydrox ylase activity was suppressed by 94 to 65% whereas aromatase activity was strongly suppressed by 72 to 17%, respectively. From our results o f high estrogen 2-hydroxylase activity in PIH placentas, it is assumed that there is a different estrogen catalyzing mechanism in PIH placen tas.