Corticosteroid 11-beta-dehydrogenase isozyme 2 (11β-HSD2)

Corticosteroid 11-beta-dehydrogenase isozyme 2 (11β-HSD2) is a NAD^+-dependent enzyme encoded by the HSD11B2 gene and primarily expressed in aldosterone-selective epithelial tissues such as kidney, colon, and salivary and sweat glands[1][5]. It catalyzes the conversion of active cortisol into inactive cortisone, thereby protecting the mineralocorticoid receptor from being non-selectively activated by glucocorticoids in tissues responsive to aldosterone[1][5]. This role is critical for maintaining electrolyte homeostasis and blood pressure, since cortisol is present at much higher concentrations than aldosterone but can activate mineralocorticoid receptors equally well without this protective enzymatic activity[1][3]. HSD11B2 activity is also essential in the placenta, where it shields the fetus from excess maternal glucocorticoids, influencing fetal growth and long-term health outcomes[2]. Inhibition or genetic deficiency of 11β-HSD2 leads to apparent mineralocorticoid excess (AME), resulting in sodium retention, hypertension, hypokalemia, and risk of cardiovascular and kidney disease[1][3][7]. Several drugs, especially some azole antifungals (itraconazole, posaconazole) and compounds found in licorice (glycyrrhetinic acid), inhibit 11β-HSD2, and such inhibition is clinically significant both in therapeutic and toxicological contexts[2][6][7].

Other names

11β-hydroxysteroid dehydrogenase 211β-HSD2HSD11B2Type 2 11β-hydroxysteroid dehydrogenase

Inhibition of enzyme activity leads to increased local cortisol, resulting in mineralocorticoid receptor activation by cortisol (and not just by aldosterone), contributing to hypertension and related conditions. Some drugs inhibit both 11β-HSD2 and other steroid-converting enzymes, affecting steroid hormone balance.