Localisation of 11 beta-hydroxysteroid dehydrogenase--tissue specific protector of the mineralocorticoid receptor.
In vitro the mineralocorticoid receptor is non-specific and does not distinguish between aldosterone and cortisol. In vivo certain tissues with this receptor are aldosterone selective (eg, kidney and parotid) whereas others with the same receptor are not (eg, hippocampus and heart). Experiments in rats showed that 11 beta-hydroxysteroid dehydrogenase (which converts cortisol to cortisone in man and corticosterone to 11-dehydrocorticosterone in the rat) was much more highly concentrated in aldosterone-selective tissues than in non-selective tissues. The localisation in the selective tissues was such that the enzyme could act as a paracrine or possibly an autocrine mechanism protecting the receptor from exposure to corticosterone. Autoradiographic studies showed that protection is lost when the enzyme is inhibited; 3H-corticosterone and 3H-aldosterone were bound to similar sites. These findings seem to explain why sodium retention, hypokalaemia, and hypertension develop in subjects with congenital deficiency of 11 beta-OHSD and those in whom the enzyme has been inhibited by liquorice.
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000450:Aldosterone / Q000493:pharmacokinetics; D000818:Animals; D001345:Autoradiography; D003345:Corticosterone / Q000493:pharmacokinetics; D005260:Female; D006624:Hippocampus / Q000201:enzymology* / Q000276:immunology; D006913:Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000302:isolation & purification*; D007672:Kidney Cortex / Q000201:enzymology* / Q000276:immunology; D007684:Kidney Tubules / Q000201:enzymology / Q000276:immunology; D008297:Male; D008901:Mineralocorticoids / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology* / Q000276:immunology; D009928:Organ Specificity / Q000187:drug effects; D010306:Parotid Gland / Q000201:enzymology* / Q000276:immunology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000378:metabolism*
D008901:Mineralocorticoids; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D003345:Corticosterone