Estrogen regulation of the cytochrome P450 3A subfamily in humans.
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.
Williams
Eric T
ET
Department of Biochemistry, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin, MSB 6.200, Houston, TX 77030, USA.
Leyk
Małgorzata
M
Wrighton
Steven A
SA
Davies
Peter J A
PJ
Loose
David S
DS
Shipley
Gregory L
GL
Strobel
Henry W
HW
D000367:Age Factors; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D016133:Polymerase Chain Reaction; D017698:Postmenopause; D017697:Premenopause; D012313:RNA / Q000187:drug effects / Q000378:metabolism
D004967:Estrogens; D012313:RNA; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human