Role of serum- and glucocorticoid-inducible kinase SGK1 in glucocorticoid regulation of renal electrolyte excretion and blood pressure

Background/Aims: The serum- and glucocorticoid-inducible kinase SGK1 was originally cloned as a glucocorticoid-regulated gene and later as a transcriptional target for mineralocorticoids. SGK1 regulates channels and transporters including the renal Na+ channel ENaC. It contributes to mineralocorticoid regulation of renal Na+ excretion and salt appetite. The present study explored the contribution of SGK1 to effects of glucocorticoids on mineral and electrolyte metabolism. Methods: SGK1-knockout mice (sgk1-/-) and their wild-type littermates (sgk1+/+) were analyzed in metabolic cages with or without treatment for 14 days with dexamethasone (3 mg/kg b.w., i.p.). Blood pressure was determined by the tail-cuff method. Results: Prior to treatment fluid intake, urinary flow rate, urinary Na+, K+, phosphate and Cl- excretion, plasma electrolyte and glucose concentrations as well as blood pressure were similar in sgk1-/- and sgk1+/+ mice. Dexamethasone did not significantly alter renal Na+, K+, Cl- and Ca2+ excretion but decreased plasma Ca2+ and phosphate concentration in sgk1+/+ mice. The effect on Ca2+ was significantly augmented and the effect on phosphate significantly blunted in sgk1-/- mice. Dexamethasone significantly increased fasting blood glucose concentrations in both genotypes. Dexamethasone increased blood pressure in sgk1+/+ mice, an effect significantly blunted in sgk1 -/- mice. Conclusions: The present observations disclose SGK1-sensitive glucocorticoid effects on calcium-phosphate metabolism and blood pressure.