Focused DNA microarray analysis for sex-dependent gene expression of drug metabolizing enzymes, transporters and nuclear receptors in rat livers and kidneys

被引:12
作者
Iwano, Shunsuke [1 ]
Higashi, Eriko [1 ]
Miyoshi, Tomoya [1 ]
Ando, Akihiro [1 ]
Miyamoto, Yohei [1 ]
机构
[1] Toray Industries Ltd, Pharmaceut Res Labs, Toxicol & Pharmacokinet Labs, Kamakura, Kanagawa 2488555, Japan
关键词
aryl hydrocarbon receptor (AhR); cytochrome P450 (CYP); DNA microarray analysis; sex-dependent gene expression; UDP glucuronosyltransferase (UGT); GROWTH-HORMONE; GENDER-DIFFERENCES; TOXICITY; PLASMA;
D O I
10.2131/jts.37.863
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Cytochrome P450(CYP)s are known to show a sexual dimorphic expression in rat livers. However, the comprehensive analysis for the sex-dependent gene expressions of drug metabolizing enzymes except for CYPs, transporters and nuclear receptors in rat livers and kidneys has not been investigated yet. The purpose of the present study was to identify the novel drug metabolizing and pharmacokinetics (DMPK)-related gene(s) which show the sex difference in the mRNA expressions in rat livers and kidneys. Total RNAs were prepared from livers and kidneys in both male and female rats (Crl:CD(SD) and Crlj:WI). A DNA microarray analysis using a "GeneSQUARE Multiple Assay DNA Microarray Drug Metabolism Gene Expression for Rat" was performed. DMPK-related genes which showed sex differences in the mRNA expression were identified in rat livers or kidneys. Especially, the female dominant expressions of UDP glucuronosyltransferase (UGT) s were seen in rat livers and kidneys. The sex difference of UGT expressions in rats might be one of the causal factors of the sex difference of the biological response to UGT substrates.
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页码:863 / 869
页数:7
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