Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 119, Issue 1-2, Pages 1-13Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2010.01.007
Keywords
11 beta-Hydroxysteroid dehydrogenase; Glucocorticoid; Steroid metabolism; Hexose-6-phosphate dehydrogenase; Detoxification; 7-Ketocholesterol; Carbonyl reductase
Funding
- Swiss National Science Foundation [31003A-124912]
- Novartis Research Foundation
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The primary function of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) is to catalyze the conversion of inactive to active glucocorticoid hormones and to modulate local glucocorticoid-dependent gene expression. Thereby 11 beta-HSD1 plays a key role in the regulation of metabolic functions and in the adaptation of the organism to energy requiring situations. Importantly, elevated 11 beta-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 11 beta-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 11 beta-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 11 beta-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 11 beta-HSD1, with a focus on cofactor and substrate specificity and on possible alternative functions of this enzyme. (C) 2010 Elsevier Ltd. All rights reserved.
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