Target tissue specificity of mineralocorticoids

Mineralocorticoid receptors have equivalent, high affinity for aldosterone and for the physiological glucocorticoids cortisol and corticosterone, which circulate at much higher concentrations. In physiologic mineralocorticoid target tissues, glucocorticoids are excluded from mineralocorticoid receptors by conversion to their receptor-inactive 11-keto metabolites, by the enzyme 11beta hydroxysteroid dehydrogenase. Aldosterone, in contrast, escapes metabolism by cyclizing its 11-OH group with the reactive -CHO at position 18. In most endocrine systems, specificity is conferred in large part by the ability of the receptor to distinguish between signal and noise. Why, for mineralocorticoid action, specificity is prereceptor-a nonmetabolized signal, and an enzyme that excludes noise-remains to be explored.