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

11-beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is a high-affinity, NAD+-dependent microsomal enzyme primarily localized in the renal collecting ducts, colon, and salivary glands [1][3]. Its fundamental biological function is the unidirectional conversion of active cortisol into inactive cortisone, which prevents cortisol from binding to the mineralocorticoid receptor (MR) [2][4]. Since cortisol and aldosterone have similar affinities for the MR, 11β-HSD2 is essential for ensuring that aldosterone can regulate sodium and potassium balance without interference from much higher circulating levels of glucocorticoids [1][2]. Genetic mutations in the HSD11B2 gene result in the syndrome of apparent mineralocorticoid excess (AME), a condition characterized by life-threatening hypertension and hypokalemia [2][3]. Pharmacological inhibition of 11β-HSD2 by compounds such as glycyrrhizic acid (found in licorice) or carbenoxolone mimics this syndrome, leading to secondary hypertension [4]. The enzyme is also expressed in the placenta, where it protects the fetus from high maternal glucocorticoid levels, playing a role in developmental programming [1][4]. Understanding 11β-HSD2 is crucial for managing secondary hypertension and evaluating the safety profiles of drugs that may inadvertently inhibit its activity [4].

Other names

Corticosteroid 11-beta-dehydrogenase isozyme 2HSD11B2HSD11K11-DH211-beta-HSD2

Inhibition of 11β-HSD2 prevents the conversion of cortisol to cortisone, leading to high local cortisol concentrations that inappropriately activate the mineralocorticoid receptor [2][4].