title: [Tissue-specific changes in cortisol metabolism and their potential role in the metabolic syndrome].
abstract: The intracellular enzyme IIbeta-hydroxysteroid dehydrogenase (IIbetaHSD) catalyses the interconversion between the biologically-active cortisol and inactive cortisone. There are two distinct isozymes: IIbetaHSD type I behaves predominantly as a reductase in vivo and activates cortisone into cortisol, whereas IIbetaHSD type 2 functions as a dehydrogenase and inactivates cortisol into cortisone. At tissue level, IIbetaHSD type I amplifies the effect ofglucocorticoids, whereby free cortisol is generated from the relative excess of circulating free cortisone. Both animal and human studies have demonstrated that alterations in IIbetaHSD type I activity in adipose tissue and liver are associated with the metabolic syndrome, thus possibly reflecting a tissue-specific (omental) Cushing's syndrome. Pharmacological inhibition of IIbettaHSD type I activity provides an interesting mechanism for the development of novel therapeutic agents for type-2 diabetes mellitus.
authors.affiliation: Universitair Medisch Centrum Groningen, afd. Endocrinologie, Postbus 30.001, 9700 RB Groningen. m.n.kerstens@int.umcg.nl
authors.forename: M N
authors.initials: MN
authors.lastname: Kerstens
authors.forename: B H R
authors.initials: BH
authors.lastname: Wolffenbuttel
authors.forename: R P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000378:metabolism; D003348:Cortisone / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D024821:Metabolic Syndrome / Q000201:enzymology*
chemical_list: D006913:Hydroxysteroid Dehydrogenases; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003348:Cortisone; D006854:Hydrocortisone