Decreased estrogen hydroxylation in male rat liver following cimetidine treatment.
Administration of cimetidine (600 mumol/kg x 5) to adult male rats resulted in 55 and 25% decreases, respectively, in estradiol 2- and 16 alpha-hydroxylation. The same treatment also decreased the activities of ethylmorphine demethylase, aryl hydrocarbon hydroxylase, aniline hydroxylase and heme oxygenase but did not inhibit the activities of 7-ethoxycoumarin de-ethylase and delta-aminolevulinic acid synthase or decrease cytochrome P-450 content. In vitro addition of cimetidine (10-300 microM) also inhibited estradiol hydroxylations, and the effect was additive in rats pretreated with cimetidine in vivo; the other enzymic activities studied were completely unaffected by in vitro addition of cimetidine. In contrast, there was no effect of cimetidine either in vivo or in vitro on any of these activities in female rats. The results point to a wide variation in the susceptibilities of different isozymes of cytochrome P-450 to inhibition by cimetidine and suggest that such differential susceptibilities are also highly dependent on the sex of the animal.
Galbraith
R A
RA
Rockefeller University Hospital, New York, NY 10021.
Jellinck
P H
PH
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002927:Cimetidine / Q000494:pharmacology*; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072467:Cytochrome P450 Family 2; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D006418:Heme / Q000378:metabolism; D006900:Hydroxylation; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D051381:Rats; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors
D006418:Heme; D004958:Estradiol; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; D019363:Cytochrome P-450 CYP1A1; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase; C020120:estrogen 2-hydroxylase