Expression and activity of the cortisol-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 is tissue and species-specific

The microsomal enzyme 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) interconverts glucocorticoid receptor-inert cortisone (11-dehydrocorticosterone in rodents) to its receptor-active form cortisol (corticosterone in rodents). Thus, 11 beta-HSD1 amplifies glucocorticoid action at the tissue level. According to the current literature, dysregulation of glucocorticoid signaling may contribute to the pathogenesis of the metabolic syndrome in which regeneration of cortisol by 11 beta-HSD1 may be an important factor. This is why the enzyme has been very intensely investigated as a potential therapeutic target to treat metabolic complications such as obesity and diabetes type 2. However, due to controversial results from the various animal and human studies as well as from different findings with regard to tissue-specific expression and activity, the varied results unfortunately do not yield a consistent picture. Therefore, the precise role of 11 beta-HSD1 in the development of complications associated with the metabolic syndrome has still not been deciphered yet. Overall, the prominent role of this enzyme in the pathogenesis of the metabolic syndrome becomes more and more dubious and therefore further studies are necessary to clarify its role finally. This short review gives an overview on the main contradicting findings on the role of 11 beta-HSD1 in the development of visceral obesity and diabetes type 2.