Interactions of mineralocorticoids and glucocorticoids in epithelial target tissues revisited.
The interplay between mineralocorticoids (MCs) and glucocorticoids (GCs) in sodium transporting epithelia is complex and only partially understood. In seminal papers published in the years soon after the discovery of aldosterone, various investigators experimentally observed that mineralocorticoid-induced renal sodium retention could only be reliably measured in adrenalectomized animals. Addition of endogenous GCs or their 11-dehydro metabolites blunted the antinatriuretic action of aldosterone and 11-dehydro-GCs decreased binding of aldosterone to mineralocorticoid receptors (MR). Under normal circumstances, endogenous GCs alone do not induce sodium transport in MC responsive epithelia yet these same GCs are able to activate MR and induce sodium transport if the enzyme 11beta-HSD2 is inhibited. Given the physiologic concentrations of both MCs and GCs, it is likely that the local epithelial cell exposure to GCs is great enough to allow GC binding to MR despite the presence of 11beta-HSD2. Thus other factors supplement the receptor selectivity role suggested for 11beta-HSD2. Why GCs bind to MR under one set of conditions and produce no effect and under different sets of conditions (11beta-HSD2 inhibition) elicit sodium transport remains a puzzle to be solved. What is clear is that a dual role for 11beta-HSD2 is emerging; first as the putative "guardian" over the MR reducing GC binding, and second as a source for 11-dehydro-GCs, which may serve as endogenously and locally produced "spironolactone-like substances", which may thus attenuate aldosterone-induced sodium transport.
Morris
David J
DJ
The Department of Laboratory Medicine, The Miriam Hospital, Brown University Medical School, Providence, RI, US. Dmorris@lifespan.org
Latif
Syed A
SA
Brem
Andrew S
AS
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D000818:Animals; D004848:Epithelium / Q000378:metabolism*; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D008901:Mineralocorticoids / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*
D005938:Glucocorticoids; D008901:Mineralocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D012964:Sodium; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2