Monooxygenase mediating catecholestrogen formation by rat anterior pituitary is an estrogen-4-hydroxylase.
Microsomes from rat anterior pituitaries (AP) were incubated with (3H)estradiol under conditions previously shown to support catecholestrogen (CE) formation by placental microsomes via an NADPH- or an organic hydroperoxide-dependent, peroxidatic mechanism. Under conditions optimized for monooxygenase activity (pH 8.0, 5 mM NADPH), 4-hydroxylation predominated (apparent Vmax = 65 pmol and 13 pmol/mg protein/30 min for 4- and 2-hydroxy-E2, respectively). Under conditions optimized for peroxidatic activity (pH 6.0, 50 mM cumene hydroperoxide) 2- and 4-hydroxylated-E2 were produced in similar amounts. Thus in the AP, unlike in other target tissues studied, NADPH-dependent CE synthetase is a 4-hydroxylase and significant 2-hydroxylation occurs only via the peroxidatic mechanism. We propose that 4-hydroxylated CEs, which are both potent, long acting estrogens and catechols, serve as local mediators of actions of phenolic estrogens on the AP.
Bui
Q D
QD
Department of Obstetrics and Gynecology, Milton S. Hershey Medical Center, Penn. State. Univ., Hershey 17033.
Weisz
J
J
D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D002393:Estrogens, Catechol / Q000096:biosynthesis*; D005260:Female; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D010052:Ovariectomy; D010903:Pituitary Gland, Anterior / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013250:Steroid Hydroxylases / Q000378:metabolism*
D002393:Estrogens, Catechol; D004958:Estradiol; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C020120:estrogen 2-hydroxylase