Administration of Xenobiotics With Anti-estrogenic Effects Results in mRNA Induction of Adult Male-Specific Cytochrome P450 Isozymes in the Livers of Adult Female Rats

Abstract

Abstract.: Cytochrome P450 (CYP) catalyzes the oxidation of many endogenous and xenobiotic compounds. The expression of CYP isozymes are modulated by endogenous hormones and xenobiotics. We found that, although CYP2C11 and CYP3A2 are adult male-specific isozymes, they are also expressed in prepubertal female Sprague Dawley (SD) rats. However, the mRNA levels for these isozymes in prepubertal female SD rats decreased over time and became undetectable at 7 weeks of age. On the other hand, ovariectomy, administration of ICI182780, a specific estrogen antagonist, or administration of lindane, which is a widely used pesticide with anti-estrogenic effects, induced these adult male-specific CYP mRNAs in adult female SD rats. These results suggest that estrogen is involved in suppression of both CYP2C11 and CYP3A2 in adult female rats. The expression of these CYP isozymes in female rats, therefore, is affected by sexual maturity and by disrupting adult female hormonal homeostasis. We also performed a field survey to examine whether the induction of CYP2C11 or CYP3A2 differs between adult female roof rats in rural and metropolitan districts. RT-PCR showed that the mRNAs for CYP2C11 and CYP3A2 were expressed in half of the adult female roof rats captured in Osaka (as a metropolitan area district) but not in those captured in Hokkaido (as a rural district). Thus, induction of the adult male-specific CYP isozymes in adult female roof rats captured in Osaka might be caused by consumption of xenobiotics with anti-estrogenic effects. Keywords:: cytochrome P450 (CYP), CYP isozyme, biomarker, adult male-specific CYP, estrogen antagonist