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

Abstract

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 Ca(2+) excretion but decreased plasma Ca(2+) and phosphate concentration in sgk1(+/+) mice. The effect on Ca(2+) 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.