11beta-HSD1, inflammation, metabolic disease and age-related cognitive (dys)function

Abstract

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is an intracellular amplifier of glucocorticoid action. By converting intrinsically inert glucocorticoids (cortisone, 11-dehydrocorticosterone) into their active forms (cortisol, corticosterone), 11beta-HSD1 increases glucocorticoid access to receptors. Glucocorticoid hormones modulate diverse physiological processes, linking circadian rhythms to food seeking, motivational and cognitive behaviours, as well as intermediary metabolism and immune responses. They are a key component of pathways that buffer the organism against stressful challenges. Here we review the part played in these processes by 11beta-HSD1, and discuss the promise of inhibitors of 11beta-HSD1 in alleviating disorders associated with cumulative stress.