[Tissue-specific changes in cortisol metabolism and their potential role in the metabolic syndrome].

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.