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 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-O-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 beta-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 micrograms 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.
Okubo
K
K
Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan.
Jinbo
M
M
Toma
Y
Y
Shimizu
Y
Y
Yanaihara
T
T
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001141:Aromatase / Q000378:metabolism*; D047072:Aromatase Inhibitors; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000201:enzymology; D006801:Humans; D006973:Hypertension / Q000201:enzymology*; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D010920:Placenta / Q000201:enzymology* / Q000648:ultrastructure; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000201:enzymology*; D013250:Steroid Hydroxylases / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D004958:Estradiol; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001141:Aromatase; D019363:Cytochrome P-450 CYP1A1; C020120:estrogen 2-hydroxylase