title: 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.
authors.affiliation: Department of Anatomy II, School of Veterinary Medicine, Azabu University, 1–17–71 Fuchinobe, Chuo, Sagamihara, Kanagawa 252–5201, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nishikawa
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Arishima
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Mitsuyuki
authors.initials: M
authors.lastname: Shirai
authors.forename: Masaru
authors.initials: M
authors.lastname: Murakami
authors.forename: Motoharu
authors.initials: M
authors.lastname: Sakaue
authors.forename: Masako
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D019362:Cytochrome P-450 CYP2B1 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D018811:Maternal Exposure; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D039181:Steroid 16-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism
chemical_list: D004968:Estrogens, Non-Steroidal; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D004054:Diethylstilbestrol; D001189:Aryl Hydrocarbon Hydroxylases; C450279:CYP2C11 protein, rat; C465138:Cyp3a23-3a1 protein, rat; D019362:Cytochrome P-450 CYP2B1; D051544:Cytochrome P-450 CYP3A; D000072467:Cytochrome P450 Family 2; D039181:Steroid 16-alpha-Hydroxylase