Pathophysiology of modulation of local glucocorticoid levels by 11β-hydroxysteroid dehydrogenases

11β-Hydroxysteroid dehydrogenases (11β HSDs) are enzymes that catalyse the interconversion of active glucocorticoids (cortisol and corticosterone) into their inactive 11-keto products (cortisone and 11-deoxycorticosterone). Two isozymes have been identified: 11β HSD type 1 is a predominant reductase, reactivating glucocorticoids from inert metabolites, whereas 11β HSD type 2 is a potent dehydrogenase, inactivating glucocorticoids. They play a major role in the modulation of local cortisol levels and hence access of active steroid to corticosteroid receptors. This review focuses on the clinical importance of 11β HSDs. We describe recent research that has not only advanced our understanding of the physiological role of these enzymes, but also their role in common diseases, including primary obesity and essential hypertension. These data provide encouragement that novel therapies will arise from a fuller understanding of the 11β HSD system.