EFFECT OF OVARIECTOMY AND ANDROGEN ON PHENOBARBITAL INDUCTION OF HEPATIC CYP2B1 AND CYP2B2 IN SPRAGUE-DAWLEY RATS

The purpose of this study was to investigate the impact of prepubertal ovariectomy and postpubertal administration of testosterone on induci bility of rat hepatic CYP2B1 and CYP2B2 by phenobarbital. Intact adult male and female Sprague-Dawley rats were injected ip with sodium phen obarbital (10 mg/kg) or saline (control) once daily on days 129-135 of age and sacrificed one day after the last dose, Hepatic microsomal an drostenedione 16 beta-hydroxylase activity, benzyloxyresorufin O-dealk ylase activity, pentoxyresorufin O-dealkylase activity, and CYP2B1 pro tein levels were lower in phenobarbital-treated female rats than in ph enobarbital-treated male rats, In contrast, there was no sex differenc e in inducibility of CYP2B2, The lesser inducibility of CYP2B1 in adul t female rats was attributed to the presence of an intact ovary becaus e prepubertal ovariectomy (day 25 of age) resulted in increased induct ion of CYP2B1 and its associated activities (androstenedione 16 beta-h ydroxylase, benzyloxyresorufin O-dealkylase and pentoxyresorufin O-dea lkylase) by phenobarbital. By comparison, postpubertal administration of testosterone enanthate (5 mu mol/kg sc once daily on days 80-94 of age) did not enhance the inducibility of CYP2B1 or its associated acti vities in prepubertally ovariectomized adult (136-day-old) rats admini stered phenobarbital (10 mg/kg/day on days 129-135 of age), However, t he androgen treatment did increase CYP2C11-dependent testosterone 2 al pha-hydroxylase activity in the same microsomal samples, Overall, the results show a sex difference in phenobarbital induction of hepatic CY P2B1 but not CYP2B2 in adult Sprague-Dawley rats, They also indicate t hat prepubertal ovariectomy enhances the effect of phenobarbital on CY P2B1, whereas administration of testosterone enanthate post-pubertally does not influence the inducibility of either CYP2B1 or CYP2B2 in pre pubertally ovariectomized adult rats.