11beta-hydroxysteroid dehydrogenase: unexpected connections

11beta-Hydroxysteroid dehydrogenase (11beta-HSD) is an enzyme system that catalyses the interconversion of active glucocorticoids to their inactive metabolites, and is now established as a crucial mechanism modulating corticosteroid hormone action. Two isozymes have been identified. In vivo, 11beta-HSD1 acts predominantly as an oxoreductase using NADP(H) as a cofactor to generate cortisol, whereas 11beta-HSD2 acts exclusively as an NAD-dependent dehydrogenase, inactivating cortisol to cortisone. Although it was first described in the late 1950s, it is only in the past ten years that interest in 11beta-HSD has increased. Alterations in its activity have been implicated in several human diseases, including hypertension, intra-uterine growth retardation and obesity. With the ever-increasing interest in 11beta-HSD, there have also been several new tissue types and disease processes in which this enzyme system has been identified. Here, we review recent research that implicates this enzyme in new diseases, including glaucoma and cancer.