Intrinsic sexually dimorphic expression of the principal human CYP3A4 correlated with suboptimal activation of GH/glucocorticoid-dependent transcriptional pathways in men.

ABSTRACT: Cytochrome P450 (CYP)3A4 is the principal and most abundant human isoform of CYP responsible for the metabolism of more than 50% of all consumed drugs and innumerable endogenous compounds. Expression of CYP3A4 is sexually dimorphic and regulated by the combined actions of GH and glucocorticoids. In the case of the rat, nearly all of the CYPs are "intrinsically" or "inherently" sexually dimorphic, meaning that the expressed sex differences are permanent and irreversible. Using primary hepatocyte cultures derived from men and women exposed to physiologic-like levels of continuous GH (the feminine circulating profile) alone, dexamethasone alone, and the combined regimen, we observed a dramatic inherent CYP3A4 sexual dimorphism (women more than men) with all treatments. The molecular basis for

SUBMITTER: Thangavel C 

PROVIDER: S-EPMC3230058 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature