Received for publication April 27, 2004.
Revised July 15, 2004.
Accepted for publication July 21, 2004.

Estrogen Regulation of the Cytochrome P450 3A Subfamily in Humans

Abstract

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 evaluated by Western immunoblot analysis of the liver samples. The human endometrial samples were from both pre-menopausal and post-menopausal women. The pre-menopausal endometrium was either in the proliferative or secretory phase, while for the post-menopausal 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 while 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.

Key words: CYP3A, Cytochrome P450, endometrium, estrogen, human, liver

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