期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 231, 期 1-2, 页码 75-85出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2004.12.005
关键词
steroid and xenobiotic receptor; CYP3A4; MDR1
The steroid and xenobiotic receptor (SXR) has been demonstrated to play an important role in the regulation of the cytochrome P450 3A4 gene (CYP3A4) and multidrug resistance gene 1 (MDR1) by both endogenous and xenobiotic substrates. SXR and its rodent ortholog PXR exhibit marked differences in their ability to be activated by xenobiotic inducers. This suggests that results obtained by rodent models may not always accurately predict responses to the same compounds in humans. SXR expression was demonstrated in the human liver and intestine, but its systemic distribution remains unknown. Therefore in this study, we first characterized the expression of SXR and its target genes CYP3A4, and MDR1 in human adult and fetal tissues using quantitative RT-PCR, immunoblotting, and combined laser capture microscopy and RT-PCR analysis. SXR mRNA and protein are expressed in adult and fetal liver, lung, kidney, and intestine. There is a close association between the expression of SXR and its target genes in all of the tissues examined. The amounts of SXR mRNA in the liver and intestine reached maximal levels in young adults (15-38 years old) and then subsequently decreased to less than half of the maximal levels with aging. These findings demonstrated age-related differences in the body's capacity to metabolize steroids and xenobiotic compounds and suggest an important role for SXR and its target genes, CYP3A4 and MDR1 in this process. (c) 2004 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据