Effect of Neonatal Exposure of 17β-Estradiol and Tamoxifen on Hepatic CYP3A Activity at Developmental Periods in Rats

抄録

  We evaluated hepatic CYP3A activity during development in male and female rats and the effect of neonatal exposure of 17β-estradiol and tamoxifen. In untreated and olive oil-treated (control) rats, hepatic CYP3A activities evaluated by erythromycin metabolism in vitro increased several-fold from age 2 to 9 weeks in males. In contrast, activity in females remained at a low and constant level from 2 to 15 weeks. Exposure of 17β-estradiol to neonates at a dose of 10 μmol/kg daily for 3 days on day 1~3 or 4~6 after birth significantly increased hepatic CYP3A activity during the developmental period in both males and females, and a greater influence was observed in females exposed during days 4~6. Pubertal exposure of 17β-estradiol (7-weeks old, 10 μmol/kg daily for 3 days) also increased hepatic CYP3A activity, but only in females. Neonatal exposure to tamoxifen (10 μmol/kg daily for 3 days) showed no appreciable effect in either males or females. In conclusion, a marked sex-difference was observed in hepatic CYP3A activity, and exposure of 17β-estradiol to neonates increased hepatic CYP3A activity during the developmental period, especially in female rats.