Mineralocorticoid receptors, both when in tissue extracts and when recombinant-derived, have equal affinity for the physiological mineralocorticoid aldosterone and for the glucocorticoids cortisol and corticosterone, which circulate at much higher concentrations than aldosterone. Such receptors are found in physiological mineralocorticoid target tissues (kidney, parotid, and colon) and in nontarget tissues such as hippocampus and heart. In mineralocorticoid target tissues the receptors are selective for aldosterone in vivo because of the presence of the enzyme 11 beta-hydroxy-steroid dehydrogenase, which converts cortisol and corticosterone, but not aldosterone, to their 11-keto analogs. These analogs cannot bind to mineralocorticoid receptors.

In vitro, Type I receptors have high and equivalent affinity for aldosterone, corticosterone and cortisol: in vivo, physiological mineralocorticoid target tissues (kidney, colon, parotid) are highly aldosterone-selective, in contrast with hippocampus and heart. In the present study we show that the mesenteric vascular arcade is similarly highly aldosterone-selective in vivo, and in vitro shows considerable levels of 11 beta OH steroid dehydrogenase activity, previously postulated as the mechanism whereby glucocorticoids are excluded from physiological mineralocorticoid receptors.

We have previously demonstrated low levels of immunoreactive

In the rat, the enzyme 11beta-hydroxysteroid dehydrogenase 2 (11betaHSD2) converts the glucocorticoid corticosterone into receptor-inactive 11-dehydrocorticosterone, thereby allowing preferential access of aldosterone to mineralocorticoid receptors (MR). The present study examines the distribution of this enzyme by in situ hybridization, using a homologous complementary RNA probe for 11betaHSD2. 11betaHSD2 messenger RNA was detected in classic epithelial aldosterone target tissues (kidney, salivary glands, and colon), the female reproductive system (ovary, oviduct, uterus, and placenta), and the adrenals; levels in heart, testis, and liver were below the limits of detection. We interpret the finding of 11betaHSD2 expression in both classical MR-containing aldosterone target tissues and a variety of other tissue as evidence that in the rat, the enzyme may play physiological roles in addition to that of excluding glucocorticoids from epithelial MR.

Abstract. Using radioimmunoassay and immunofluorescence with antibodies to fl-endorphin (3EP)