Estrogen regulation of the cytochrome P450 3A subfamily in humans
Estrogen regulation of the cytochrome P450 3A subfamily in humans
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DOI：
10.1124/jpet.104.068908
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发表时间：
2004-11-01
影响因子：
3.5
通讯作者：
Strobel, HW
中科院分区：
文献类型：
--
作者：
Williams, ET;Leyk, M;Strobel, HW
本研究探讨了雌激素在调节人类 CYP3A 亚家族（CYP3A4、CYP3A5、CYP3A7 和 CYP3A43）表达中的可能作用。为了实现这一目标，对人类肝脏和子宫内膜样本中的 mRNA 进行了定量，并通过肝脏样本的蛋白质免疫印迹分析评估了总 CYP3A 蛋白水平。人类子宫内膜样本来自绝经前和绝经后妇女。绝经前子宫内膜处于增殖期或分泌期，而对于绝经后子宫内膜样本，女性接受了安慰剂或雌激素替代品艾司托哌酯治疗。经过分析，CYP3A4 mRNA 在女性肝脏中的表达量低于男性。在子宫内膜中，CYP3A4和CYP3A43被雌激素下调，而CYP3A5在分泌期表达水平较高。子宫内膜中未检测到 CYP3A7。此外，CYP3A 亚家族在肝脏中的 mRNA 表达随着年龄的增加而增加。总CYP3A蛋白和总CYP3A mRNA的表达水平表现出良好的相关性。尽管雌激素对 CYP3A4 mRNA 表达有明显的调节作用，但雌激素的作用可能会被其他基因表达调节剂所掩盖。
This study examines the possible role of estrogen in regulating the expression of the human CYP3A subfamily: CYP3A4, CYP3A5, CYP3A7, and CYP3A43. To accomplish this goal, mRNA was quantified from human livers and endometrial samples, and total CYP3A protein levels were evaluated by Western immunoblot analysis of the liver samples. The human endometrial samples were from premenopausal and postmenopausal women. The premenopausal endometrium was either in the proliferative or secretory phase, whereas for the postmenopausal endometrium samples, the women had been treated with either a placebo or estropipate, an estrogen substitute. After analyses, CYP3A4 mRNA was shown to have lower hepatic expression in females than in males. In the endometrium, CYP3A4 and CYP3A43 are down-regulated by estrogen, whereas CYP3A5 is expressed at higher levels during the secretory phase. CYP3A7 was not detected in the endometrium. In addition, the CYP3A subfamily showed increased mRNA expression in the liver as age increased. The expression levels of total CYP3A protein and total CYP3A mRNA showed good correlation. Despite apparent regulation of CYP3A4 mRNA expression by estrogen, the effects of estrogen may be overshadowed by additional regulators of gene expression.