[11beta-hydroxysteroide dehydrogenases. Recent advances].
11beta-hydroxysteroide dehydrogenase (11beta-OHSD) enzymes exhibit a regulating action upon cortisol metabolism before access to its receptors. Two types of isoenzymes have been described, type 2 being the most anciently known. Type 2 11beta-OHSD, which changes cortisol into cortisone, is a unidirectional dehydrogenase mainly located in kidney, that protects mineralocorticoid receptors from illicit activation by glucocorticoids. Mutations of the gene coding for this enzyme has been demonstrated in apparent mineralocorticoid excess, which induces hypertension and hypokalemia with low renin and aldosterone levels. Polymorphisms of this gene could modulate essential hypertension and also be responsible for certain forms of acquired apparent mineralocorticoid excess especially after liquorice intoxication, in hypothyroidism, Cushing syndrome, and chronic renal insufficiency. Type 1 11beta-OHSD, which changes cortisone into cortisol, is a reductase, mainly located in liver and adipose tissue. Functional defects of this enzyme have been shown in polycystic ovaries and cortisone reductase deficiency. By contrast, metabolic syndrome, corticoid-induced osteoporosis, and glaucoma are linked to a local over-activity of this enzyme. The understanding of action mechanisms of these two enzymes currently leads to 11beta-OHSD inhibitors development, therefore opening new therapeutic strategies, especially in metabolic syndrome.
Vantyghem
M-C
MC
Service d'endocrinologie et métabolisme, clinique d'endocrinologie Marc-Linquette, 6, rue du Professeur-Laguesse, CHRU de Lille, 59037 Lille cedex, France. mc-vantyghem@chru-lille.fr
Marcelli-Tourvieille
S
S
Defrance
F
F
Wemeau
J-L
JL
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D042842:11-beta-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D003480:Cushing Syndrome / Q000201:enzymology; D005260:Female; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D007668:Kidney / Q000201:enzymology*; D010641:Phenotype; D011085:Polycystic Ovary Syndrome / Q000201:enzymology / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000502:physiology
D018161:Receptors, Mineralocorticoid; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D042842:11-beta-Hydroxysteroid Dehydrogenases; D006854:Hydrocortisone