Epithelial Sodium adsorption in the lung is dependent on expression of the epithelial sodium channel ENaC and this is regulated through glucacorticoid hormones and the serum and glucacortoid regulated kinase SGK1. Parallel electrophysiological experiments have shown that treatment with dexamethasone, a synthetic glucacorticoid and SGK1 can both independently establish a sodium adsorbing phenotype in H441 human airway epithelial cells (see SG Brown et al, this symposium). It has been suggested that SGK1 regulates sodium transport through the regulation of a-ENaC transcription (Boyd C. & A. Naray-Fejes- Toth Am. J. Physiol.-Lung Cell Mol. Physiol. 288: F505-F512) To test this hypothesis a 2.3kb fragment containing the a ENaC promoter was cloned into a luciferase reporter and transfected into H441 cells in combination with either a constitutively active form of SGK1 or dexamethasosne. This demonstrated that while dexamethasone could drive expression from the a-ENaC promoter the expression of SGK1 alone could not. Mutation of the glucacorticoid response element (GRE) in the a-ENaC promoter demonstrated that this element was solely responsible for dexamethasone enhanced transcription from this promoter. Thus while the expression of SGK1 and dexamethasone can both establish a sodium adsorbing phenotype in H441 cells they do so by separate mechanisms.