title: Gender differences in serum and glucocorticoid regulated kinase-1 (SGK-1) expression during renal ischemia/reperfusion injury.
abstract: 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.
authors.affiliation: First Department of Pediatrics, Semmelweis University, Budapest, Bókay u. 53-54. 1083, Hungary. rusai@gyer1.sote.hu
authors.forename: Krisztina
authors.initials: K
authors.lastname: Rusai
authors.forename: Agnes
authors.initials: A
authors.lastname: Prókai
authors.forename: Beáta
authors.initials: B
authors.lastname: Szebeni
authors.forename: Krisztina
authors.initials: K
authors.lastname: Mészáros
authors.forename: Andrea
authors.initials: A
authors.lastname: Fekete
authors.forename: Balázs
authors.initials: B
authors.lastname: Szalay
authors.forename: Ádám
authors.initials: Á
authors.lastname: Vannay
authors.forename: Peter
authors.initials: P
authors.lastname: Degrell
authors.forename: Veronika
authors.initials: V
authors.lastname: Müller
authors.forename: Tivadar
authors.initials: T
authors.lastname: Tulassay
authors.forename: Attila J
authors.initials: AJ
authors.lastname: Szabó
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D002460:Cell Line; D017931:DNA Primers; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply*; D008297:Male; D008856:Microscopy, Fluorescence; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000201:enzymology*; D012737:Sex Factors; D013739:Testosterone / Q000494:pharmacology; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D017931:DNA Primers; D004967:Estrogens; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D013739:Testosterone; D000099184:Serum-Glucocorticoid Regulated Kinases