11-beta-hydroxysteroid dehydrogenase (11β-HSD) (11β-HSD)

11-beta-hydroxysteroid dehydrogenases (11β-HSD) are enzymes that regulate the local availability of glucocorticoids by catalyzing the interconversion of active cortisol and inactive cortisone (Chapman et al., 2013, Physiological Reviews). The family includes two main isoforms: 11β-HSD1, which primarily regenerates cortisol from cortisone in the liver and adipose tissue, and 11β-HSD2, which inactivates cortisol in the kidney to protect the mineralocorticoid receptor from illicit activation (White et al., 1997, Endocrine Reviews). 11β-HSD1 is a key target in metabolic research because its overexpression is linked to obesity, insulin resistance, and type 2 diabetes (UniProt P28845). In contrast, 11β-HSD2 deficiency or inhibition results in apparent mineralocorticoid excess, a condition characterized by severe hypertension and hypokalemia (StatPearls, "Apparent Mineralocorticoid Excess"). Therapeutic development has focused on selective 11β-HSD1 inhibitors, such as Xanamem and SPI-62, to treat metabolic syndrome and cognitive impairment without affecting the protective role of 11β-HSD2 (PubMed, PMID: 31433057).

Other names

11-beta-hydroxysteroid dehydrogenaseCorticosteroid 11-beta-dehydrogenase11-beta-HSDHSD11B

Inhibition of the enzymatic conversion between active glucocorticoids (cortisol) and inactive 11-keto metabolites (cortisone), thereby modulating local tissue glucocorticoid concentrations (Chapman et al., 2013, Physiological Reviews).