11β-Hydroxysteroid Dehydrogenase-2 and Salt-Sensitive Hypertension.

1335 Glucocorticoid intracellular metabolism, catalyzed by the 2 isozymes of 11β-hydroxysteroid dehydrogenase (11βHSD), determines the corticosteroid action on target tissues. 11β-HSD1 functions as a reductase in most cells and catalyzes the regeneration of active glucocorticoids, thereby amplifying their action. This isozyme is widely expressed in liver, adipose tissue, muscle, pancreatic islets, and adult brain. 11β-HSD2 is a high-affinity dehydrogenase and inactivates cortisol and corticosterone to the inert product, cortisone. Cortisone in turn can be reactivated through reduction by 11β-HSD1 (Figure 1). The 11β-HSD2 isozyme is highly expressed in the distal nephron and, as we learn here, in the nucleus tractus solitarius. 11β-HSD2 serves to protect the mineralocorticoid receptor (MR) from occupation by cortisol or corticosterone (Figure 2).