Mineralocorticoid receptors: Emerging complexity and functional diversity

Mineralocorticoid receptor (MR) activation in renal epithelial cells in response to the binding of aldos terone has long been implicated In the maintenance of body salt and fluid homeostasis and blood pressure control. 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) is believed to confer specificity, on aldosterone to activate MR by inactivating 11 beta-hydroxyglucocorticoids (corticosterone, cortisol) that are 100-1000 times more abundant in plasma than aldosterone and that can also hind and activate MR. Increasing evidence, however, challenges such a simple view of MR activation as well as its interaction with glucocorticoids and 11 beta-HSDs. In non-epithelial tissues including brain, cardiomycetes and macrophages, 11 beta-hydroxyglucocorticoids seem to act as MR antagonists, and redox changes and the naling events may play pivotal roles for receptor activation in these tissues. This review addresses the emerging new view of the complex mechanisms underlying MR specificity of action, with a diversity of physiological roles and functions in different mineralocorticoid-responsive tissues. (C) 2008 Elsevier Inc. All rights reserved