Effects of the estrous cycle and the gender difference on hepatic drug-metabolising enzyme activities

The aim of the present study was to investigate the effects of the estrous cycle and physiological dose of estradiol (E₂) and the gender difference on several hepatic drug-metabolising enzyme activities. Eight-week old female Sprague-Dawley rats at different stages of the estrous cycle [proestrous (P), estrous (E), and diestrous (D)] and 8-week old male rats were used in this study (n = 5, respectively). Serum E₂ level at D was higher than that at E and lower than that at P. The hepatic cytochrome P450 content, aniline hydroxylase, ethoxycoumarin O-deethylase and aminopyrine N-demethylase activities in male were significantly higher than those in female at any stage of the estrous cycle and these activities in female remained unchanged during the estrous cycle. Neither the estrous cycle nor the gender difference affected the cytochrome b₅ content. NADPH-cytochrome c reductase (fP(Υ)) activity at P was similar to that in male, and was significantly higher than that in E and D. fP(Υ) activity was increased by the administration of physiological dose of E₂ in ovariectomized rats. Uridine diphosphate glucuronyltransferase (UDP-GT) activity at E was significantly lower than that at P or D and that activity in female was significantly lower than that in male. These results indicate that the estrous cycle, especially serum E₂ level, may affect both fP(Υ) and UDP-GT activities.