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Review
. 2010 Jan;95(1):13-8.
doi: 10.1113/expphysiol.2008.045914. Epub 2009 Jul 31.

The mammalian mineralocorticoid receptor: tying down a promiscuous receptor

Elise P Gomez-Sanchez  1
Affiliations
Review

The mammalian mineralocorticoid receptor: tying down a promiscuous receptor

Elise P Gomez-Sanchez. Exp Physiol. 2010 Jan.

Abstract

The mineralocorticoid receptor (MR) has been called a promiscuous receptor because its intrinsic affinity for aldosterone, cortisol and corticosterone is similar. Since glucocorticoids circulate in concentrations 100- to 1000-fold those of aldosterone, stoichiometry dictates that MR should be activated by glucocorticoids, not aldosterone, yet MRs are expressed in many tissues and regulate diverse functions, many of them under the regulation of the renin-angiotensin-aldosterone system. A relatively small number of brain MRs are aldosterone selective and modulate blood pressure. Evidence for possible mechanisms conferring ligand specificity in the context of mineralocorticoid-induced hypertension and the brain are discussed. These include factors (or mechanisms) intrinsic to the receptor, such as alternative splice variants and translation start sites, and extrinsic to the MR, including differential access through the blood-brain barrier, differential recruitment of co-regulators and scaffolding proteins, 11beta-steroid dehydrogenase activity, synthesis of potent acylated aldosterone derivatives and the synthesis of relevant amounts of aldosterone in areas of the brain that modulate blood pressure.

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