11β-Hydroxysteroid Dehydrogenase Type 1 and the Metabolic Syndrome

In the past few years, efforts are being made to unravel the mechanisms endowed with the metabolic disturbances associated with obesity that predispose to the metabolic syndrome (MetSyn). The special pathogenic role of liver and visceral adipose tissue (VAT) functions has been particularly intriguing, and many hypotheses have been advanced to explain this association. Tissue-specific actions of glucocorticoids (GCs) go far beyond the circulating levels of the hormones and can be controlled by local intracellular enzymes. In the past few years, evidence is being gathered not only on the relevance of such enzymes to GC physiological actions but also on their involvement in the pathophysiology of certain chronic disease states, in which circulating GC levels are not necessarily altered. These enzymes are 11┚-hydroxysteroid dehydrogenases (11┚-HSDs, EC 1.1.1.146) which interconvert inactive GCs, such as cortisone and dehydrocorticosterone, and the active hormones, cortisol and corticosterone.