The specificity of the human mineralocorticoid receptor: clinical clues to a biological conundrum.

Data from in vitro studies show that the mineralocorticoid receptor has an equal affinity for cortisol and aldosterone. This contrasts with the well known selectivity of aldosterone for binding to tissues such as the kidney despite the much higher circulating levels of glucocorticoids. This paper puts forward the hypothesis that the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) is responsible for determining this selectivity. Congenital or acquired deficiency of this enzyme results in a failure of the normal protective mechanism by which cortisol is converted to cortisone or corticosterone to 11-dehydrocorticosterone. As a result the receptor is exposed to cortisol or corticosterone in high concentration which results in sodium retention and potassium loss. In contrast the hippocampal type 1 receptor is associated with much lower 11 beta-OHSD activity and is thus not aldosterone-selective.