11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2)

11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2) is an NAD⁺-dependent enzyme that catalyzes the conversion of active glucocorticoids (cortisol) into their inactive forms (cortisone), thereby regulating the access of glucocorticoids to the mineralocorticoid receptor[1][2][3][4]. It is highly expressed in aldosterone-sensitive epithelial tissues such as kidney, colon, salivary glands, and sweat glands, as well as in the placenta and certain brain regions[1][3][4]. 11β-HSD2 protects aldosterone-selective tissues from cortisol-induced activation of the mineralocorticoid receptor, ensuring normal sodium and water balance and blood pressure control[1][2][3]. Genetic deficiency or pharmacological inhibition (e.g., by licorice derivatives) of 11β-HSD2 results in apparent mineralocorticoid excess, with symptoms of hypertension, hypokalemia, and suppressed renin and aldosterone production[1][4]. The enzyme also has a protective role during fetal development in the placenta and developing brain. Its activity is clinically relevant for the pharmacokinetics of corticosteroid drugs and can play a role in cancer metastasis[5][9].

Other names

Corticosteroid 11-beta-dehydrogenase isozyme 2Hydroxysteroid 11-beta dehydrogenase 2HSD11B2Type-2 11β-hydroxysteroid dehydrogenase

Enzyme inhibition (e.g., by glycyrrhetinic acid or carbenoxolone) leads to increased local cortisol, overstimulating mineralocorticoid receptors with consequent sodium retention, hypokalemia, and hypertension[1][4][5] - Metabolism of glucocorticoid drugs: oxidation of steroid drugs by 11β-HSD2 affects their pharmacodynamic profile[5]