Interactions of mineralocorticoids and glucocorticoids in epithelial target tissues

Abstract

Background. In Na+-transporting epithelial target tissues, such as mammalian kidney and the isolated toad bladder, glucocorticoids (GCs) do not normally elicit Na+ retention. In mammalian kidney, however, they do cause kaliuresis. The presence of 11β-hydroxysteroid dehydrogenase isoform 2 (11β-HSD2) in these target tissues inactivates the GCs, preventing them from accessing mineralocorticoid receptors (MRs) and stimulating Na+ transport. Results. The usually observed Na+ retention elicited by the mineralocorticoid aldosterone was blunted when the GC corticosterone was coadministered along with aldosterone. However, when corticosterone was administered along with a 11β-HSD2 inhibitor, a strong Na+ transport was elicited by an MR-mediated mechanism. 11-Dehydrocorticosterone also blunted aldosterone-elicited Na+ transport in these target tissues. Conclusions. 11β-HSD2 appears to play two important roles in the epithelial target tissues, kidney and toad bladder. The first is to protect GC access to MR, and the second involves the product of the enzyme to regulate the magnitude of aldosterone-induced Na+ retention.