Publication

Journal	The Journal of steroid biochemistry and molecular biology
Volume (Issue)	119(1-2)
Page(s)	1 - 13
Title of proceedings	The Journal of steroid biochemistry and molecular biology
DOI	10.1016/j.jsbmb.2010.01.007

The primary function of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is to catalyze the conversion of inactive to active glucocorticoid hormones and to modulate local glucocorticoid-dependent gene expression. Thereby 11beta-HSD1 plays a key role in the regulation of metabolic functions and in the adaptation of the organism to energy requiring situations. Importantly, elevated 11beta-HSD1 activity has been associated with metabolic disorders, and recent investigations with rodent models of obesity and type 2 diabetes provided evidence for beneficial effects of 11beta-HSD1 inhibitors, making this enzyme a promising therapeutic target. Several earlier and recent studies, mainly performed in vitro, revealed a relatively broad substrate spectrum of 11beta-HSD1 and suggested that this enzyme has additional functions in the metabolism of some neurosteroids (7-oxy- and 11-oxyandrogens and -progestins) and 7-oxysterols, as well as in the detoxification of various xenobiotics that contain reactive carbonyl groups. While there are many studies on the effect of inhibitors on cortisone reduction and circulating glucocorticoid levels and on the transcriptional regulation of 11beta-HSD1 in obesity and diabetes, only few address the so-called alternative functions of this enzyme. We review recent progress on the biochemical characterization of 11beta-HSD1, with a focus on cofactor and substrate specificity and on possible alternative functions of this enzyme.