Congenital and acquired syndromes of apparent mineralocorticoid excess.
The enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) interconverts cortisol and cortisone. Congenital deficiency of the renal isoform of the enzyme results in hypertension, hypokalemia and suppression of the renin-angiotensin-aldosterone system--the apparent mineralocorticoid excess syndrome (AME). In these patients cortisol acts as a potent mineralocorticoid. Suppression of plasma cortisol with dexamethasone results in natriuresis, potassium retention and reduction in blood pressure. Ingestion of excess liquorice or taking carbenoxolone produces an acquired form of AME. The active component of liquorice is glycyrrhetinic acid (GE) and carbenoxolone is the hemisuccinate derivative. Both GE and carbenoxolone are potent inhibitors of 11 beta-OHSD. In vitro studies have shown that 11 beta-OHSD is present in aldosterone-selective tissues and acts as an autocrine mechanism which prevents cortisol from gaining access to the non-specific mineralocorticoid receptor (MR). Congenital or acquired absence of this enzyme allows cortisol to bind to MR resulting in AME. 11 beta-OHSD also appears to be important in controlling cortisol access to glucocorticoid receptors. Variable placental 11 beta-OHSD may alter foetal exposure to maternal cortisol and affect growth as indicated by the correlation between foetal weight and placental 11 beta-OHSD. Thus the tissue-specific distribution, ontogeny and modulation of this enzyme allows it to dictate glucocorticoid effects in addition to its key role in ensuring the specificity of the MR.
Department of Medicine, Western General Hospital, Edinburgh, Scotland.
C R
CR
Edwards
B R
BR
Walker
R
R
Benediktsson
J R
JR
Seckl
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000818:Animals; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000172:deficiency*; D008901:Mineralocorticoids / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000378:metabolism; D013577:Syndrome
D008901:Mineralocorticoids; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases