Mineralocorticoid selectivity: Molecular and cellular aspects

Aldosterone acts in mineralocorticoid-sensitive cells by binding to the mineralocorticoid receptor (MR). Because the MR displays similar affinity for aldosterone and glucocorticoid hormones and because these latter hormones are 100- to 1000-fold more abundant than aldosterone in the plasma, mechanisms are required to avoid permanent illicit occupancy of MR by glucocorticoid hormones. The main mechanism of mineralo-corticoid selectivity is enzymatic: the 11 beta hydroxysteroid dehydrogenase (HSD2) metabolizes glucocorticoid hormones into derivatives with a low affinity for MR. The cell biology and regulation of HSD2 are reviewed in this article. as well as its implications in human hypertension. Other factors play a role in mineralocorticoid selectivity: the MR itself. the possibility to form homodimers (MR-MR), or heterodimers (with the glucocorticoid receptor). All of these cellular events participate to successive dynamic equilibriums, which allow fine tuning of transcriptional regulation of target genes, depending on the target tissue and the hormonal status.