Effects of gonadectomy and sex hormones on the induction of hepatic CYP4A by clofibrate in rats.
The effects of sex hormones on the induction of hepatic CYP4A by clofibrate were examined in intact and gonadectomized rats of both sexes by measuring the activity of lauric acid omega-hydroxylation (LAH). Although the specific activity of LAH is the same in both sexes, only in male rats, was the activity significantly increased by administration of clofibrate. In female rats, ovariectomy or testosterone treatment resulted in an enhanced response to clofibrate, similar to that observed in male rats. In ovariectomized female rats, the effect of clofibrate was decreased by estradiol. In orchiectomized male rats, testosterone had no effect on the induction of LAH by clofibrate and estradiol suppressed induction. Changes in LAH activities co-related well with those in CYP4A proteins and CYP4A1 mRNA. These results suggest that some factors associated with female sex hormones were involved in the suppressive regulation of CYP4A induced by clofibrate.
Hiratsuka
M
M
Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Matsuura
T
T
Sato
M
M
Suzuki
Y
Y
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D002994:Clofibrate / Q000494:pharmacology*; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004579:Electron Transport / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006900:Hydroxylation; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007850:Lauric Acids / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D006899:Mixed Function Oxygenases / Q000096:biosynthesis*; D009919:Orchiectomy; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar
D012739:Gonadal Steroid Hormones; D000960:Hypolipidemic Agents; D007850:Lauric Acids; C030358:lauric acid; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D042926:Cytochrome P-450 CYP4A; D002994:Clofibrate