Glutamyl cycle in the rat liver appears to be sex-gender specific

Abstract

Numerous studies show sexually dimorphic responses of drug metabolizing enzymes in the liver, but it is less clear whether xenobiotic detoxification mediated by glutathione is sex-gender specific. Therefore, we investigated whether sex-gender differences exist in the biosynthesis and metabolism of GSH in the rat liver. Livers were obtained from Sprague-Dawley rats of both sexes for measurement of glutathione, its precursors and metabolites by capillary electrophoresis, whereas H(2)S and malondialdehyde were measured by colorimetric assays. The expression of glutamylcysteine ligase (GCL), the key enzyme in glutathione synthesis was detected by Western blotting and immunohistochemistry. It was observed that L-methionine, glutathione, taurine and malondialdehyde (a marker of lipid peroxidation) were similar in livers from both sexes, while L-cysteine levels were significantly higher and H(2)S was lower in female rat livers. Furthermore, L-methionine and L-cysteine, L-cysteine and glutathione, L-cysteine and taurine were positively associated only in male livers. Finally, the female liver expressed less GCL than the male liver. These data suggest that the glutamyl cycle in the liver is sexually dimorphic. This difference could be linked to the increased sensitivity of females to drugs and xenobiotics.