Aldosterone Receptors and Their Renal Effects: Molecular Biology and Gene Regulation

GOMEZ-SANCHEZ, C, GOMEZ-SANCHEZ, E.P., GALIGNIANA, M.D.

Textbook of Nephro-Endocrinology

Elsevier

Lugar: San Diego; Año: 2009; p. 329 - 348

The primary sites of action of aldosterone in the kidney are in the epithelial cells of the distal portions of the nephron.  It binds and activates the mineralocorticoid receptor, a member of the ligand-dependent family of nuclear transcription regulators to initiate the transcription of genes encoding multiple proteins that enable and enhance the vectorial transport of sodium and water from the filtrate in the lumen to the extracellular space.  Chief among these are proteins that increase the number of functional epithelial sodium channels intercalated in the luminal side of the tubular epithelial cell. One of the first and most prominent genes to be transcribed is that for Sgk1, a serine-threonine kinase.   Among the most prominent functions of Sgk1 is the phosphorylation of Nedd4-2, a ubiquitin ligase, thereby inhibiting the ubiquitylation, thus targeting for proteosomal degradation, of the PY domains of the b and g epithelial sodium channel subunits.  Phosphorylation of the repressor molecule AF9 by Sgk1 impairs its ability to hypermethylate H3 histone, allowing the mineralocorticoid receptor to bind the ENaCá promoter and initiate á subunit transcription.  Aldosterone also has important rapid non-genomic effects on cell signaling cascades that participate in the nephron in sodium transport.