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Submitted on January 5, 2006
Accepted on March 6, 2006
Division of Cell and Molecular Biology, Department of Biology, Boston University, Boston, MA 02215, U.S.A.
* To whom correspondence should be addressed. E-mail: djw{at}bu.edu.
The liver is a primary target for the action of growth hormone (GH), a pituitary protein hormone that regulates a broad range of physiological processes, including long bone growth, fatty acid oxidation, glucose uptake and hepatic steroid and foreign compound metabolism. GH exerts sex-dependent effects on the liver in many species, with many hepatic genes, most notably genes coding for cytochrome P450 (CYP) enzymes, being transcribed in a sex-dependent manner. Sex differences in CYP expression are most striking in rats and mice (up to 500-fold male-female differences), but are also seen, albeit to a much smaller degree, in humans, where they are an important determinant of the sex-dependence of hepatic drug and steroid metabolism. This article examines the mechanisms whereby GH, via its sex-dependent temporal patterns of pituitary release, activates intracellular signaling leading to the sexually dimorphic transcription of CYPs and other liver-expressed genes. Recent findings implicating the GH-regulated transcription factor STAT5b, hepatocyte nuclear factors 3
, 4
and 6, and sex differences in DNA methylation and chromatin structure in the sex-dependent actions of GH are reviewed and current mechanistic models are evaluated.
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