Mineralocorticoid target genes

Classically, aldosterone activates mineralocorticoid receptors, which then act as ligand-dependent transcriptional regulators of target genes. The mechanism of action of aldosterone in both epithelial and nonepithelial tissues is not well understood. This review summarizes recent studies on a number of candidate mineralocorticoid target genes that are activated within hours after physiologic levels of aldosterone are reached. These include the genes for the subunits of the epithelial sodium channel and Na⁺K⁺ATPase pump and genes coding for three proteins (a serine/threonine kinase SGK1; a small guanosine triphosphate (GTP)-binding protein K-Ras2A; and channel-inducing factor or CHIF) that regulate Na⁺ channel activity in epithelia. The authors discuss evidence for induction by aldosterone of the angiotensin II AT1 receptor gene in the heart, which may contribute to the fibrotic response of the heart to elevated aldosterone and salt.