This contribution is about mineralocorticoid receptors (MRs) in their capacity as mediators of glucocorticoid action in the brain. This paradox has evolved because MRs are promiscuous and bind with high-affinity cortisol and corticosterone as well as aldosterone, deoxycorticosterone, and progesterone. The MRs “see,” however, predominantly glucocorticoids, because of their 100–1000-fold excess over aldosterone; bioavailability is further enhanced because of local regeneration of glucocorticoids by 11βOH-steroid dehydrogenase (HSD-1). In contrast to these glucocorticoid-preferring MR, the evolutionary later appearance of aldosterone-selective MR in epithelial cells depends on co-localization with the oxidase 11β-hydroxysteroid-dehydrogenase type 2 (HSD-2) in a few hundred neurons in the nucleus tractus solitarii (NTS), which innervate frontal brain regions to regulate cognitive, emotional, and motivational aspects of salt appetite. The glucocorticoid-MRs and classical glucocorticoid receptors (GRs) mediate in a complementary manner the glucocorticoid coordination of circadian events and mediate the regulation of stress coping and adaptation. If an individual is exposed to a threat, MRs are crucial for the selection of a particular coping style, which is via GR activation subsequently stored in the memory for future use. Our contribution is concluded with the notion that an imbalance in MR- and GR-mediated actions increases susceptibility to stress-related disorders.
Part of the book: Aldosterone-Mineralocorticoid Receptor