Global expression profiles have identified >1,000 genes that are sex-differentially expressed in mouse liver and impact numerous physiological and pathophysiological processes. These genes are regulated by sex-dependent plasma GH patterns, with male-specific genes suppressed and female-specific genes induced in livers of male mice given GH by continuous infusion (female-like GH profile). Mouse knockout studies have identified the GH-activated transcription factor STAT5b and the liver-enriched transcription factor HNF4alpha as essential for liver sex differences, however, the precise mechanisms through which these factors regulate liver sexual dimorphism have remained elusive. Recent findings evidence dynamic, sex-dependent STAT5 binding to liver chromatinin vivo in direct response to each plasma GH pulse, while time course studies reveal an unanticipated complexity in the sex-specific responses to GH. Finally, major advances have been made with the development and analysis of high quality global DNase hypersensitivity (DHS) maps for mouse liver and the discovery of >1000 sex-dependent DHS sites, many of which are responsive to sex-specific changes in plasma GH status and likely to contain regulatory sequences that mediate the sex-specific actions of GH on liver gene expression.
