Involvement of testosterone in the induction of hepatic microsomal cytochrome P-450 2B1/2 (P-450 2B1/2) by 1-benzylimidazole in male and female rats: sex-differentiated induction of P-450 2B1/2 species.
We examined the effect of 1-benzylimidazole on the induction of cytochrome P-450 1A1/2 (P-450 1A1/2) and cytochrome P-450 2B1/2 (P-450 2B1/2) in normal, castrated, ovariectomized and hypophysectomized male rats, and in castrated rats treated with testosterone. 1-Benzylimidazole markedly increased P-450 content in male and female rats. Parallel to the dose-dependent increase in P-450 content, 1-benzylimidazole produced a significant increase in P-450 2B1/2 in male rats, but not in female rats. 1-Benzylimidazole failed to induce P-450 2B1/2 in castrated male and ovariectomized female rats. Treatment of castrated male rats with testosterone restored the induction of P-450 2B1/2 by 1-benzylimidazole. Treatment of ovariectomized female rats with 1-benzylimidazole or phenobarbital led to the increase in P-450 content, accompanying by the induction of P-450 2B1/2 by the latter treatment, but not the former. In hypophysectomized male rats, 1-benzylimidazole was able to induce P-450 2B1/2 in contrast to castrated male rats. Neonatal male and female rats responded well to the induction of P-450 2B1/2 by 1-benzylimidazole. The present findings suggest that P-450 2B1/2 induction by 1-benzylimidazole would be coupled with circulating testosterone regulated by hypophysis-testis axis. 1-Benzylimidazole produced sex-differentiated induction of P-450 2B1/2 in pubertal rats, but not in neonatal animals. The present findings would be provide information on a unique effect of 1-benzylimidazole on P-450 2B1/2 induction in rats.
Kobayashi
Y
Y
Showa College of Pharmaceutical Sciences, Tokyo, Japan.
Yoshida
T
T
Kotani
E
E
Aoyagi
T
T
Kuroiwa
Y
Y
Tobinaga
S
S
D000818:Animals; D000831:Animals, Newborn; D001189:Aryl Hydrocarbon Hydroxylases; D002369:Castration; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D007016:Hypophysectomy; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013250:Steroid Hydroxylases / Q000096:biosynthesis*; D013739:Testosterone / Q000494:pharmacology*
D007093:Imidazoles; D013739:Testosterone; C017062:1-benzylimidazole; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C025619:steroid 16-beta-hydroxylase