Major molecular differences between mammalian sexes are involved in drug metabolism and renal function

Dev Cell. 2004 Jun;6(6):791-800. doi: 10.1016/j.devcel.2004.05.005.


Many anatomical differences exist between males and females; these are manifested on a molecular level by different hormonal environments. Although several molecular differences in adult tissues have been identified, a comprehensive investigation of the gene expression differences between males and females has not been performed. We surveyed the expression patterns of 13,977 mouse genes in male and female hypothalamus, kidney, liver, and reproductive tissues. Extensive differential gene expression was observed not only in the reproductive tissues, but also in the kidney and liver. The differentially expressed genes are involved in drug and steroid metabolism, osmotic regulation, or as yet unresolved cellular roles. In contrast, very few molecular differences were observed between the male and female hypothalamus in both mice and humans. We conclude that there are persistent differences in gene expression between adult males and females. These molecular differences have important implications for the physiological differences between males and females.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • DNA / analysis
  • DNA / genetics
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation / genetics*
  • Genitalia / cytology
  • Genitalia / metabolism*
  • Humans
  • Hypothalamus / cytology
  • Hypothalamus / metabolism
  • Kidney / cytology
  • Kidney / metabolism*
  • Liver / cytology
  • Liver / metabolism*
  • Male
  • Metabolic Clearance Rate / genetics
  • Mice
  • Oligonucleotide Array Sequence Analysis
  • Organ Specificity
  • Ovary / cytology
  • Ovary / metabolism
  • Pharmaceutical Preparations / metabolism*
  • Receptors, Cell Surface / genetics
  • Serpins
  • Sex Characteristics*
  • Testis / cytology
  • Testis / metabolism
  • Transcortin


  • Pharmaceutical Preparations
  • Receptors, Cell Surface
  • SERPINA6 protein, human
  • Serpins
  • DNA
  • Transcortin