Molecular Pharmacology of the Youngest Member of the Nuclear Receptor Family: The Mineralocorticoid Receptor

Abstract

The mineralocorticoid receptor (MR) was the last member of the nuclear receptor superfamily to evolve. It is responsible for the maintenance of the water and salt homeostasis. Like most ligand-activated transcription factors of this superfamily, it is activated by ligand binding. The MR exists as a large heterocomplex assembled with the heat-shock protein of 90-kDa chaperone, Hsp90, and other associated chaperones and cochaperones. The composition of this heterocomplex is affected by the nature of the bound steroid. MR biological responses are also affected by the redox status of the cell or due to protein phosphorylation. In this chapter, the conformational requirements of the steroid to become an optimal MR ligand, the role of the Hsp90-based heterocomplex, and the influence of MR modifications by oxidation and phosphorylation is discussed. These properties are analyzed in the light of the relevance of this nuclear receptor as a key pharmacological target for disorders mostly related to the hydroelectrolytic homeostasis.