Acute regulation by corticosteroids of channel-inducing factor gene messenger ribonucleic acid in the distal colon

The molecular mechanisms by which corticosteroids affect fluid and electrol yte balance are unclear. Though gluco corticoid-responsive genes have been identified, genes regulated by aldosterone have not. CHIF (channel-inducing factor gene) is a recently identified gene that is up-regulated in the dis tal colon by chronic corticosteroid exposure, is expressed in the kidney, a nd induces a K+-specific current in Xenopus oocytes. The predicted protein shows similarity to gamma Na.K-ATPase, phospholemman, and Mat-8; all seem t o be involved in ion transport. CHIF thus presents as a potential aldostero ne target gene. In this study, CHIF expression was examined in rats in the acute timeframe of 0.5-4 h after corticosteroid administration. CHIF messen ger RNA showed up-regulation by both mineralocorticoid and glucocorticoid r eceptor agonists in the distal colon, which was not diminished by cyclohexi mide. Corticosteroid regulation was not observed in the kidney. Basal and i nduced expression was absent in the lung and in all gastrointestinal tissue s except colon, with expression increasing proximal to distal. CHIF is the first gene to show acute regulation by aldosterone and thus encodes a candi date aldosterone-induced protein. In addition, gamma Na.K-ATPase gene expre ssion was found to be very low in colon and significantly higher in kidney. Regulation by corticosteroids was not evident in either tissue.