How Can Aldosterone Act as a Mineralocorticoid?

The circulating levels of glucocorticoid hormones are commonly several orders of magnitude higher than those of the mineralocorticoid aldosterone. Paradoxically, cytosol Type I receptors from a variety of tissues, or recombinant-derived human kidney mineralocorticoid receptors, have essentially indistinguishable affinity for aldosterone, corticosterone and cortisol. In vivo, however, though injected corticosterone and aldosterone are equivalently taken up and retained by rat hippocampus or heart, binding of corticosterone is very much lower in classical mineralocorticoid target tissues (kidney, parotid, colon). The genesis of this aldosterone-selectivity in vivo appears to be the expression, in physiologic mineralocorticoid target tissues, of the microsomal enzyme 11β hydroxysteroid dehydrogenase (11βOHSD). Whereas cortisol and corticosterone have affinity for Type I receptors equivalent to