Sex-specific differences in gene expression related to drug metabolism and hypertension

06/03/04

Many obvious physical and hormonal differences exist between men and women, and now researchers have discovered that there are major molecular differences as well. A new research study published in the June issue of Developmental Cell reveals that there are striking sex-specific patterns of gene expression that will likely provide critical insight into documented physiological differences, including sex-specific risk for disease.

Although there have been reports of differences in gene expression between males and females, there has not been a comprehensive study examining multiple tissue types. Dr. Michael Snyder from the Department of Molecular Biophysics and Biochemistry at Yale University and colleagues used a sophisticated genetic screening technique to look for molecular differences between mammalian sexes in multiple tissues. The researchers surveyed nearly 14,000 genes in the kidney, liver, and reproductive organs as well as in a brain region called the hypothalamus. "We looked for genes that were expressed in both sexes but significantly higher in one sex relative to the other and genes with expression detected only in one sex," explains Dr. Snyder. "We want to build a comprehensive map of the genetic and molecular differences between males and females. This map can be navigated to find insight into diseases known to have sex-specific propensities (e.g. anemia, hypertension, and renal dysfunction)."

Significant differences in gene expression were observed in the mouse liver, kidney, and reproductive tissues. Many of the differentially expressed genes were involved in drug and steroid metabolism and regulation of fluid balance. The results have interesting implications for explaining how males and females respond differently to drug treatments and sex-specific propensities for high blood pressure. Interestingly, the adult hypothalamus had very few sex-specific genes, despite its role as the control center for behavior. This was not only the case in the mouse, but in the human brain as well. "It is possible that sexual differences in the adult hypothalamus are mediated by a small number of genes or genes that are expressed transiently," hypothesizes Dr. Snyder.

These results demonstrate that many sex-specific differences exist in adult mammals. According to Dr. Snyder, "The differences in gene expression reported here were observed well after puberty, demonstrating that they are important for routine physiological differences between mature males and females. We are currently looking at molecular differences between males and females at multiple developmental stages, including puberty, as well as differences in subpopulations of cells within a tissue."

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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