Disinhibitory pathways for control of sodium transport: regulation of ENaC by SGK1 and GILZ

Am J Physiol Renal Physiol. 2006 Oct;291(4):F714-21. doi: 10.1152/ajprenal.00061.2006. Epub 2006 May 23.


Regulation of ENaC occurs at several levels. The principal hormonal regulator of ENaC, aldosterone, acts through the mineralocorticoid receptor to modulate ENaC-mediated sodium transport, and considerable attention has focused on defining the components of the early phase of this response. Two genes, SGK1 and GILZ, have now been implicated in this regulation. While the functional significance of SGK1 in mediating aldosterone effects is well established, new evidence has enhanced our understanding of the mechanisms of SGK1 action. In addition, recent work demonstrates a novel role for GILZ in the stimulation of ENaC-mediated sodium transport. Interestingly, both SGK1 and GILZ appear to negatively regulate tonic inhibition of ENaC and thus use disinhibition to propagate the rapid effects of aldosterone to increase sodium reabsorption in tight epithelia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Epithelial Sodium Channels
  • Humans
  • Immediate-Early Proteins / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Sodium / metabolism*
  • Sodium Channels / physiology*
  • Transcription Factors / metabolism*


  • Epithelial Sodium Channels
  • Immediate-Early Proteins
  • Sodium Channels
  • TSC22D3 protein, human
  • Transcription Factors
  • Sodium
  • Protein-Serine-Threonine Kinases
  • serum-glucocorticoid regulated kinase