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(Hypertension. 2006;48:1018.)
© 2006 American Heart Association, Inc.

Editorial Commentaries

Aldosterone and Mineralocorticoid Receptors

Lessons From Gene Deletion Studies

John W. Funder

From the Prince Henry’s Institute of Medical Research, Clayton, Victoria, Australia.

Correspondence to John W. Funder, Prince Henry’s Institute of Medical Research, PO Box 5152, Clayton, Victoria, Australia 3168. E-mail john.funder@princehenrys.org

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Currently, aldosterone and mineralocorticoid receptors (MR) are generally thought of as cognate ligand and receptor, except perhaps by the neuroscientists. This fidelity is essentially true for aldosterone, which has high affinity for MR, much lower affinity for glucocorticoid receptors (GR), and negligible affinity for other nuclear transactivating factors. A number of in vitro studies requiring micromolar concentrations of aldosterone, on the principle that if a little is good, a lot must be better, have been interpreted as evidence for physiological mineralocorticoid actions. These are commonly effects mediated via GR; no (patho)physiology in vivo can realistically be ascribed to aldosterone via GR or any other nuclear receptor. Many, but perhaps not all, nongenomic effects of aldosterone are mediated via classic MR¹: in terms of genomic and, very possibly, nongenomic effects, aldosterone, thus, seems to solely address a particular receptor.

The same, however, is not the case for MR, which bind aldosterone, deoxycorticosterone, corticosterone, cortisol, and progesterone with essentially the same high affinity. This versatility, the >1000-fold higher circulating glucocorticoid levels and the finding of high levels of MR in such improbable aldosterone target tissues as the hippocampus, provides grounds for suspicion that MR may entertain more binding partners than aldosterone alone. These clearly include the physiological glucocorticoids, in both nonepithelial and epithelial tissue,² and possibly progesterone in tissues such as placenta.³ The roles of such binding, in the brain^4,5 and elsewhere,^6,7 are currently part of the ongoing re-evaluation of the nonaldosterone (patho)physiology of MR.

This fundamental difference is highlighted by . . . [Full Text of this Article]

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