Aldosterone regulates a 5' variant sgk1 transcript via a shared hormone response element in the sgk1 5' regulatory...

We previously identified a 5' variant alternate transcript of Sgk1 (Sgk1_v3) encoding an NH₂-terminal variant Sgk1 isoform, Sgk1_i3 that, like Sgk1, is expressed in the distal convoluted tubule, connecting tubule and collecting duct and can stimulate epithelial Na⁺ transport (Am J Physiol Renal Physiol 303: F1527-F1533, 2012). We now demonstrate that, similar to Sgk1, aldosterone and glucocorticoids stimulate Sgk1_v3 expression in cell lines from the collecting duct and airway epithelia. In mice, short term aldosterone infusion and maneuvers that increase endogenous aldosterone secretion including dietary Na⁺ deprivation and K⁺ loading increases distal nephron Sgk1_v3 expression in vivo. Although Sgk1_v3 has a different 5' proximal regulatory region from Sgk1, the transcription start sites are less than 1000 bp apart. We cloned the 5' regulatory region for Sgk1 and Sgk_v3 upstream of a luciferase gene and by deletion and reporter gene analysis we localized the corticosteroid regulatory region for Sgk1_v3 to a glucocorticoid response element (GRE) that had previously been identified for Sgk1 (Am J Physiol Endo Metab 283: E971-E979, 2002). We tested this element with MR in an MR-null cell line and demonstrate that aldosterone stimulates Sgk1 and Sgk1_v3 via this GRE We conclude that corticosteroids stimulate Sgk1 and Sgk1_v3 expression in epithelial cells via activation of a common conserved GRE in the 5' flanking region of Sgk1.