The sgk, an aldosterone-induced gene in mineralocorticoid target cells, regulates the epithelial sodium channel

Aldosterone increases sodium reabsorption in tight epithelia. The early pha se of this stimulatory effect is thought to involve activation of apical so dium channels. To identify immediate-early genes that initiate this effect, we used a combination of polymerase chain reaction-based subtractive hybri dization and differential display techniques. This review summarizes our re cent findings. Aldosterone rapidly increases mRNA levels of a putative Ser/ Thr kinase, sgk (or (s) under bar erum- and glucocorticoid-regulated (k) u nder bar inase), in the native mineralocorticoid target cells, that is, in cortical collecting duct (CCD) cells. The induction of sgk mRNA occurs with in 30 minutes of the addition of aldosterone and does not require de novo p rotein synthesis, indicating that sgk is an immediate/early aldosterone-ind uced gene. Induction of sgk by aldosterone is mediated through mineralocort icoid receptors (MRs), since it is prevented by ZK91857, an MR antagonist, but not by RU486, a glucocorticoid antagonist. In addition to aldosterone. RU28362, a pure glucocorticoid receptor agonist, also induced sgk mRNA, bot h in primary cultures of rabbit CCD cells and in the M-1 mouse CCD cell lin e. Sgk mRNA levels are also influenced by changes in the osmolality of the medium. In M-1 cells, incubation of cells for one hour in a mildly hypotoni c medium decreased sgk mRNA levels, whereas incubation in hypertonic medium brought about opposite changes. To determine whether sgk is involved in th e regulation of the epithelial sodium channel (ENaC). we coexpressed the fu ll-length sgk cRNA in Xenopus oocytes with the three ENaC subunits. Express ion of sgk resulted in a significant increase in the amiloride-sensitive Na current, suggesting that this protein kinase plays an important role in th e early phase of aldosterone-stimulated Na transport. These results indicat e that sgk is an aldosterone-induced immediate/early gene in native MR targ et cells. and is involved in the regulation of ion transport and possibly c ell volume.