11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2) (11-beta-HSD2)

11-beta-hydroxysteroid dehydrogenase type 2 (11-beta-HSD2) is a microsomal enzyme that plays a critical role in regulating the access of glucocorticoids to the mineralocorticoid receptor (MR) [1, 2]. It primarily functions as an oxidoreductase that converts active cortisol into inactive cortisone in humans (or corticosterone to 11-dehydrocorticosterone in rodents), utilizing NAD+ as a cofactor [4, 8]. This inactivation is essential in aldosterone-sensitive tissues, such as the kidney, colon, and salivary glands, where the MR has equal affinity for cortisol and aldosterone [3, 5, 7]. By degrading local cortisol, 11-beta-HSD2 prevents the much more abundant glucocorticoid from inappropriately activating the MR, thereby ensuring that aldosterone remains the primary regulator of sodium and potassium balance [2, 6]. Mutations in the HSD11B2 gene lead to the syndrome of apparent mineralocorticoid excess (AME), characterized by severe hypertension and hypokalemia [1, 5, 16]. Additionally, the enzyme is highly expressed in the placenta, where it protects the developing fetus from high levels of maternal glucocorticoids [1, 15]. Pharmacological inhibition of 11-beta-HSD2 by substances like glycyrrhetinic acid (found in licorice) or certain antifungal drugs can induce a state of pseudohyperaldosteronism [3, 6, 14].

Other names

11-beta-hydroxysteroid dehydrogenase type IICorticosteroid 11-beta-dehydrogenase isozyme 2NAD-dependent 11-beta-hydroxysteroid dehydrogenaseHSD11B211-DH2AMEHSD2SDR9C3

11-beta-hydroxysteroid dehydrogenase type 2 is primarily targeted by inhibitors that prevent the conversion of active cortisol to inactive cortisone [3, 6]. This inhibition leads to an accumulation of local cortisol, which then binds to and activates the mineralocorticoid receptor, mimicking the effects of aldosterone excess and resulting in sodium retention and potassium depletion [2, 5, 17].