Abstract
Mineralocorticoid receptors (MR) are found not only in classical aldosterone target tissues (kidney, colon, parotid) but also non-epithelial tissues such as hippocampus. In addition, MR have equivalent affinity for cortisol (in the rat corticosterone) as for aldosterone, which circulates at very much lower levels. Aldosterone occupancy of MR in physiologic target tissues but not hippocampus reflects the activity in these tissues of the enzyme llμ-hydroxysteroid dehydrogenase (11HSD), which converts cortisol and corticosterone to receptor-inactive 11-keto congeners; aldosterone escapes equivalent metabolism as its C11-OH is stably cyclized with the very reactive aldehyde group at C18. Studies currently in progress in this area include (1) characterization of the NAD-dependent 11HSD species (11HSD2) operant in renal distal tubule distinct from the cloned enzyme (11 ESDI) expressed in proximal tubule, testis, liver and lung; (2) exploration of the physiologic roles of ‘MR’ in hippocampus, where they are occupied by cortisol/corticosterone, and function as high-affinity glucocorticoid receptors; (3) recognition of the basis for MR and GR specificity at the transcriptional level, by oncogene product binding and/or response element differences; (4) investigation of the evolutionary basis for non-selective MR by comparative studies on guinea pigs and hamsters, and (5) further studies of the molecular mechanisms underlying the resistance syndrome of pseudohypoaldosteronism, in which independent laboratories have failed to find sequence abnormalities in the coding region of MR cDNA in different kindred with absent receptor binding.
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Funder, J. MINERALOCORTICOID RECEPTORS. Pediatr Res 33 (Suppl 5), S12 (1993). https://doi.org/10.1203/00006450-199305001-00053
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DOI: https://doi.org/10.1203/00006450-199305001-00053