PT  - JOURNAL ARTICLE
AU  - Thomas K. H. Chang
AU  - Mellissa D. Anderson
AU  - Stelvio M. Bandiera
AU  - Gail D. Bellward
TI  - Effect of Ovariectomy and Androgen on Phenobarbital Induction of Hepatic CYP2B1 and CYP2B2 in Sprague-Dawley Rats
DP  - 1997 Aug 01
TA  - Drug Metabolism and Disposition
PG  - 994--1000
VI  - 25
IP  - 8
4099  - http://dmd.aspetjournals.org/content/25/8/994.short
4100  - http://dmd.aspetjournals.org/content/25/8/994.full
SO  - Drug Metab Dispos1997 Aug 01; 25
AB  - The purpose of this study was to investigate the impact of prepubertal ovariectomy and postpubertal administration of testosterone on inducibility of rat hepatic CYP2B1 and CYP2B2 by phenobarbital. Intact adult male and female Sprague-Dawley rats were injected ip with sodium phenobarbital (10 mg/kg) or saline (control) once daily on days 129–135 of age and sacrificed one day after the last dose. Hepatic microsomal androstenedione 16β-hydroxylase activity, benzyloxyresorufin O-dealkylase activity, pentoxyresorufinO-dealkylase activity, and CYP2B1 protein levels were lower in phenobarbital-treated female rats than in phenobarbital-treated male rats. In contrast, there was no sex difference in inducibility of CYP2B2. The lesser inducibility of CYP2B1 in adult female rats was attributed to the presence of an intact ovary because prepubertal ovariectomy (day 25 of age) resulted in increased induction of CYP2B1 and its associated activities (androstenedione 16β-hydroxylase, benzyloxyresorufin O-dealkylase and pentoxyresorufinO-dealkylase) by phenobarbital. By comparison, postpubertal administration of testosterone enanthate (5 μmol/kg sc once daily on days 80–94 of age) did not enhance the inducibility of CYP2B1 or its associated activities in prepubertally ovariectomized adult (136-day-old) rats administered phenobarbital (10 mg/kg/day on days 129–135 of age). However, the androgen treatment did increase CYP2C11-dependent testosterone 2α-hydroxylase activity in the same microsomal samples. Overall, the results show a sex difference in phenobarbital induction of hepatic CYP2B1 but not CYP2B2 in adult Sprague-Dawley rats. They also indicate that prepubertal ovariectomy enhances the effect of phenobarbital on CYP2B1, whereas administration of testosterone enanthate postpubertally does not influence the inducibility of either CYP2B1 or CYP2B2 in prepubertally ovariectomized adult rats. The American Society for Pharmacology and Experimental Therapeutics