Hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1)

Hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1) is a microsomal enzyme of the short-chain dehydrogenase/reductase family, prominently expressed in the liver, adipose tissue, and central nervous system. It catalyzes the reversible conversion of the inactive steroid cortisone to the active hormone cortisol, thereby amplifying local glucocorticoid signaling. The enzyme also participates in oxysterol and bile acid metabolism, and is implicated in the pathophysiology of obesity, insulin resistance, and other metabolic disorders. It is considered a validated therapeutic target, with pharmacological inhibition explored for the treatment of metabolic syndrome, depression, and neurodegeneration. Known inhibitors include carbenoxolone, glycyrrhizic acid, and experimental agents such as emestedastat. Genetic variants and altered regulation of HSD11B1 are implicated as biomarkers for metabolic disease risk. Therapeutic challenges include the risk of cortisol insufficiency and pleiotropic effects in multiple tissues.

Other names

11-beta-hydroxysteroid dehydrogenase 1HSD11B1HSD11HSD11LSDR26C111-DH11-beta-HSD17-oxosteroid reductaseCorticosteroid 11-beta-dehydrogenase isozyme 1Short chain dehydrogenase/reductase family 26C member 1CORTRD2HDLDHI1

Inhibition of 11-beta-reductase activity (reduces local cortisol production). Downregulation of HSD11B1 expression (e.g., by salicylate/aspirin). Prevention of cortisone reactivation to cortisol.