Regulation of aromatic oxidation of estradiol-17 beta in maternal hepatic, fetal hepatic and placental tissues: comparative effects of a series of inducing agents.
The effects of nine separate inducers of cytochrome P-450-dependent monooxygenases on the hydroxylation of estradiol-17 beta (E2) were investigated in near-term pregnant rats. Isosafrole exhibited highly effective inducing properties in the maternal liver (20-fold and 5-fold increases in 4- and 2-hydroxylase activities respectively). Pregnenolone 16 alpha-carbonitrile produced approx 20- and 30-fold increases in measured respective rates of 4- and 2-hydroxylase activities in fetal hepatic tissues; isosafrole produced only 2-fold increases in the same reaction. Only minor changes or slight increases in estrogen hydroxylation rates were observed in maternal hepatic, fetal hepatic or placental tissues following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or other potent 3-methylcholanthrene (MC)-like inducing agents (beta-naphthoflavone, MC, caffeine). Phenobarbital exhibited relatively weak inducing properties and exposure of pregnant rats to ethanol from days 3-19 of gestation was without statistically significant effects on the parameters investigated. Rat placentas exhibited extremely low estrogen hydroxylase activities irrespective of pre-exposure of pregnant rats to the inducers studied. The results suggested separate regulatory controls for estrogen 2- and 4-monooxygenase activities even though relatively high correlation between the two reaction were generally observed in all three tissues.
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001571:Benzoflavones / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine); D019363:Cytochrome P-450 CYP1A1; D004958:Estradiol / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000196:embryology / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D010920:Placenta / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011247:Pregnancy; D011285:Pregnenolone Carbonitrile / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012451:Safrole / Q000494:pharmacology; D013250:Steroid Hydroxylases / Q000378:metabolism; D019324:beta-Naphthoflavone
D001140:Aroclors; D001571:Benzoflavones; D000072317:Polychlorinated Dibenzodioxins; D020111:Chlorodiphenyl (54% Chlorine); D011285:Pregnenolone Carbonitrile; D000431:Ethanol; D004958:Estradiol; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; D013250:Steroid Hydroxylases; D019363:Cytochrome P-450 CYP1A1; C020120:estrogen 2-hydroxylase; D012451:Safrole; C015959:isosafrole; D010634:Phenobarbital