Sex-dependent liver gene expression is extensive and largely dependent upon signal transducer and activator of transcription 5b (STAT5b): STAT5b-dependent activation of male genes and repression of female genes revealed by microarray analysis

Mol Endocrinol. 2006 Jun;20(6):1333-51. doi: 10.1210/me.2005-0489. Epub 2006 Feb 9.


Sexual dimorphism in mammalian liver contributes to sex differences in physiology, homeostasis, and steroid and foreign compound metabolism. Many sex-dependent liver genes are regulated by sex differences in pituitary GH secretion, with the transcription factor, signal transducer and activator of transcription (STAT5b), proposed to mediate signaling by the pulsatile, male plasma GH profile. Presently, a large-scale gene expression study was conducted using male and female mice, wild type and Stat5b inactivated, to characterize sex differences in liver gene expression and their dependence on STAT5b. The relative abundance of individual liver RNAs was determined for each sex-genotype combination by competitive hybridization to 23,574-feature oligonucleotide microarrays. Significant sex differences in hepatic expression were seen for 1603 mouse genes. Of 850 genes showing higher expression in males, 767 (90%) were down-regulated in STAT5b-deficient males. Moreover, of 753 genes showing female-predominant expression, 461 (61%) were up-regulated in STAT5b-deficient males. In contrast, approximately 90% of the sex-dependent genes were unaffected by STAT5b deficiency in females. Thus: 1) STAT5b is essential for sex-dependent liver gene expression, a characteristic of approximately 1600 mouse genes (4% of the genome); 2) male-predominant liver gene expression requires STAT5b, or STAT5b-dependent factors, which act in a positive manner; and 3) many female-predominant liver genes are repressed in males in a STAT5b-dependent manner. Several of the STAT5b-dependent male genes encode transcriptional repressors; these may include direct STAT5b targets that repress female-predominant genes in male liver. Several female-predominant repressors are elevated in STAT5b-deficient males; these may contribute to the major loss of male gene expression seen in the absence of STAT5b.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Liver / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • STAT5 Transcription Factor / deficiency
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism*
  • Sex Characteristics


  • Repressor Proteins
  • STAT5 Transcription Factor
  • Stat5b protein, mouse