11-beta-hydroxysteroid dehydrogenase 1 (11β-HSD1)

“Cortisol metabolism” generally refers to the enzymatic processes that interconvert active cortisol and inactive cortisone, as well as subsequent reductions and oxidations by A-ring reductases and cytochrome P450 enzymes. The principal enzyme for therapeutic targeting is **11β-hydroxysteroid dehydrogenase 1 (11β-HSD1)**, which catalyzes conversion of cortisone to active cortisol, regulating local glucocorticoid action in liver, adipose tissue, and other organs[1][2][3][5]. Abnormal 11β-HSD1 activity has been linked to obesity, metabolic syndrome, and type 2 diabetes, making it a focus for drug development. Drug candidates targeting 11β-HSD1 aim to lower tissue cortisol levels and ameliorate metabolic disease[2][3][5]. Other relevant enzymes in cortisol metabolism include **11β-hydroxysteroid dehydrogenase 2 (11β-HSD2)** (which inactivates cortisol), **5α-reductase/5β-reductase** (irreversible reduction), and **cytochrome P450 3A4** (hydroxylation/clearance)[1][5][7].

Other names

11-beta-hydroxysteroid dehydrogenase type 111β-HSD1HSD11B1

Inhibition of 11β-HSD1 decreases local conversion of cortisone (inactive) to cortisol (active), reducing intracellular glucocorticoid action, which may lower hepatic glucose production and improve metabolic profiles in obesity and type 2 diabetes[2][3][5].