Aromatase and Estrogen 2-Hydroxylase Activities of Human Placental Microsomes in Pregnancy-Induced Hypertension.

Abstract

Abstract. 2-Hydroxylationis one of the major metabolic pathways of estrogens and is believed to be catalyzed by a form of cytochrome P450. Recently it has been reported that estrogen 2-hydroxylase activity in human placenta is catalyzed by aromatase.Some investigators suggested the effect of catechol estrogen on human placental steroidogenesis which may be related to pregnancy-induced hypertension (PIH) through the inhibition of catechol-0-methyltransferase (COMT) activity. In order to better understand the interrelationship between placental aromatase and estrogen 2-hydroxylase activities in PIH patients, both activities were evaluated in the PIH placentas.Human placental microsomes obtained from PIH patients were incubated with [1/3-3H]androstenedione or [2-3H]estradiol in the presence of NADPH. Aromatase and estrogen 2-hydroxylase activities were assessed by the tritium water method. The immunosuppression patterns of both activities due to monoclonal antiaromatase cytochrome P450 antibody (MAb3-2C2) were studied. Estrogen 2-hydroxylase activity was significantly higher in PIH placentas (4.7 ± 0.9 pmol/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 µg IgG of MAb3-2C2, estrogen 2-hydroxylase activity was suppressed by 94 to 65% whereas aromatase activity was strongly suppressed by 72 to 17%, respectively. From our results of high estrogen 2-hydroxylase activity in PIH placentas, it is assumed that there is a different estrogen catalyzing mechanism in PIH placentas.

Oxidation of Dihydrotestosterone by Human Cytochromes P450 19A1 and 3A4

“…These latter two compounds were also found in vivo. Estrone 2-hydroxylation and the conversion of 19-norandrostenedione to estrone had previously been reported as reactions of horse (39,40) and human P450 19A1 preparations (35,36,41). We confirmed these reactions with our purified recombinant P450 19A1 (Fig.…”