The role of SGK1 in hormone-regulated sodium transport

Ion transport in epithelia is regulated by a variety of hormonal and nonhor monal factors, including mineralocorticoids, insulin, shear stress and osmo tic pressure. In mammals, the mineralocorticoid aldosterone is the principa l regulator of sodium homeostasis and hence is central to the control of ex tracellular fluid volume and blood pressure. Aldosterone acts through a mem ber of the nuclear receptor superfamily, the mineralocorticoid receptor (MR ),to control the transcriptional activity of specific target genes. Recentl y, a serine/threonine kinase, SGK1 (serum and glucocorticoid-regulated kina se isoform 1) was identified as a candidate mediator of aldosterone action in the colon and distal nephron. The aldosterone-activated MR increases SGK 1 gene transcription and SGK1, in turn, strongly stimulates the activity of the epithelial sodium channel (ENaC). Interestingly, other factors appear to regulate SGK1 gene expression and kinase activity, Insulin, for example, stimulates SGK1 activity (but not gene transcription) through its effects on phosphatidylinositol-3-kinase and osmotic shock appears to stimulate bot h SGK1 activity and gene transcription. Hence, SGK1 might integrate the eff ects of multiple hormonal and nonhormonal regulators of Na+ transport in ti ght epithelia and thereby play a key role in volume homeostasis. It is inte resting to speculate that SGK1 might be implicated in medical conditions, s uch as the insulin resistance syndrome, hypertension and congestive heart f ailure.