11β-HSD1 is the major regulator of the tissue-specific effects of circulating glucocorticoid excess
Abstract
Glucocorticoids are widely prescribed for their anti-inflammatory properties but have Cushingoid side effects that contribute significantly to patient morbidity and mortality. Here we present data to demonstrate that the adverse side-effect profile associated with exogenous active glucocorticoid (GC) administration (including glucose intolerance, hyperinsulinemia, hypertension, hepatic steatosis, increased adiposity, and myopathy) is prevented by global deletion of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in mice. This study not only defines a significant shift in our understanding of the physiological and molecular mechanisms underpinning the adverse side effects associated with GC use but also raises the possibility of targeting 11β-HSD1 as a novel adjunctive therapy in the treatment of Cushing syndrome.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- June 2014
- DOI:
- 10.1073/pnas.1323681111
- Bibcode:
- 2014PNAS..111E2482M