Rapid upregulation of serum and glucocorticoid-regulated kinase (sgk) geneexpression by corticosteroids in vivo

The molecular mechanisms by which corticosteroids regulate epithelial sodiu m transport remain to be fully elucidated. Expression of the serum and gluc ocorticoid-regulated kinase (sgk) has recently been reported to be regulate d acutely by corticosteroids in the amphibian AG cell line and in cortical collecting tubule cells in vitro. In order to extend this observation to a mammalian system in vivo, the acute response of the sgk gene to a single pa renteral dose of aldosterone or dexamethasone was examined in the rut kidne y and distal colon. The sgk mRNA levels were significantly elevated by both steroids by 30 min in the distal colon, reaching a peak at 2 h. A more mod est increase in sgk mRNA levels was also seen in the kidney in response to both steroids. In both tissues,. sgk mRNA has a very short half-life. As fo r other corticosteroid-regulated genes, the response appears to be mediated by both the mineralocorticoid and glucocorticoid receptors. The response t o aldosterone in the distal colon in the presence of cycloheximide was supe rinduced, strongly suggesting that this is a primary response. The response s to both adrenalectomy and carbenoxolone sodium treatment suggest that the observed responses to corticosteroids can occur in the physiological range of endogenous circulating corticosteroids. These studies provide strong ev idence that sgk is an aldosterone-induced gene in vivo in a mammalian syste m. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.