Maternal exposure to low doses of DES altered mRNA expression of hepatic microsomal enzymes in male rat offspring

Abstract

Our previous studies demonstrated that prenatal diethylstilbestrol (DES) treatment disrupts steroidogenesis but induces high-level expression of androgen receptor (AR) mRNA to inhibit the disruption of spermatogenesis. This study examined which prenatal DES treatment influenced hepatic microsomal enzymes, CYP3A1, CYP2B1/2, CYP2C11, UGT2B1 (UDP-glucuronosyltransferase 2B1), and IGF-1 (insulin-like growth factor-1), in male rat offspring. DES treatment decreased the mRNA expression levels of CYP3A1 and CYP2B1/2, but did not alter the expression of CYP2C11. At 6 weeks, DES treatment increasd the mRNA expression levels of UGT2B1 and IGF-1. These results suggest that prenatal DES treatment alters two hepatic enzymes (CYP3A1 and CYP2B1/2) and IGF-1 mRNA expression levels to counteract the low level of testosterone, but this disrupted UGT2B1 mRNA expression reduces the testosterone level.