Gender differences in serum and glucocorticoid regulated kinase-1 (SGK-1) expression during renal ischemia/reperfusion injury

Cell Physiol Biochem. 2011;27(6):727-38. doi: 10.1159/000330081. Epub 2011 Jun 17.


Several studies reported sexual dimorphism in the signaling mechanisms of renal ischemia/reperfusion (I/R). The anti-apoptotic serum and glucocorticoid-regulated kinase-1 (SGK-1) is up-regulated and has a significant protective role in renal I/R. SGK-1 has several target molecules, and inhibition of the inducible nitric oxide synthase (iNOS) transcription is one of its effector mechanisms. The objective of the present study was to examine if there is a gender-specific expression and activation of SGK-1 during renal I/R injury. In vitro, treatment of HK-2 kidney proximal tubular cells with different concentrations of 17-beta estradiol had no effect, whereas testosterone increased SGK-1 abundance in a dose-dependent manner. In vivo, in a rat model of unilateral renal I/R injury, there was a higher SGK-1 expression and phosphorylation in males 2 and 24 h after ischemia paralleled by reduction in the mRNA expression of iNOS compared to females. Deprivation of testosterone by castration of males resulted in decreased SGK-1 protein level at all time-points and reduced phosphorylation 2 and 24 h after reperfusion. Our results suggest that testosterone up-regulates SGK-1 in the kidney contributing to sexual dimorphisms in the cell signalling machinery. The significance of the testosterone-regulated SGK-1 level and activity in the kidney needs further investigations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Blotting, Western
  • Cell Line
  • DNA Primers
  • Estrogens / pharmacology
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Immediate-Early Proteins / genetics
  • Immediate-Early Proteins / metabolism*
  • Kidney / blood supply*
  • Male
  • Microscopy, Fluorescence
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Reperfusion Injury / enzymology*
  • Sex Factors
  • Testosterone / pharmacology


  • DNA Primers
  • Estrogens
  • Immediate-Early Proteins
  • Testosterone
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase