Early aldosterone action: toward filling the gap between transcription and transport.
The mineralocorticoid hormone aldosterone stimulates transcellular Na+ reabsorption across target epithelia after a lag period of 20 to 60 min by first activating preexisting channels (epithelial sodium channels, ENaC) and pumps (Na-K-ATPase) and, subsequently, increasing the overall transport capacity of the cells. Both these early regulatory and late anabolic-type actions depend on the transcriptional regulation exerted by hormone-activated mineralocorticoid and/or glucocorticoid receptors (MR and/or GR). Starting at the transcriptional side of the aldosterone action, recent studies have identified the small G protein K-Ras2 and the kinase sgk as the first early aldosterone-induced gene products potentially regulating Na+ transport. At the level of the Na+ transport effectors, much knowledge about ENaC and Na-K-ATPase structure-function relationship and regulation has accumulated. However, the regulatory pathway(s) that link the transcriptional action of aldosterone to these Na+ transport proteins is still to a large extent unknown. The available data suggest that the early regulatory action of aldosterone is pleiotropic, similarly to the late anabolic-type action. The early Na+ transport stimulation would be mediated by the rapid induction of gene products belonging to the regulatory network that integrates the inputs of diverse pathways and finally controls the function of the Na+ transport machinery.
Verrey
F
F
Institute of Physiology, University of Zurich, CH-8057 Zurich, Switzerland. verrey@physiol.unizh.ch
D000450:Aldosterone / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D011905:Genes, ras / Q000502:physiology; D006801:Humans; D012964:Sodium / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D014158:Transcription, Genetic / Q000502:physiology*
D000450:Aldosterone; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase