| First Author | Morgan SA | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 24 | Pages | E2482-91 |
| PubMed ID | 24889609 | Mgi Jnum | J:211636 |
| Mgi Id | MGI:5575798 | Doi | 10.1073/pnas.1323681111 |
| Citation | Morgan SA, et al. (2014) 11beta-HSD1 is the major regulator of the tissue-specific effects of circulating glucocorticoid excess. Proc Natl Acad Sci U S A 111(24):E2482-91 |
| abstractText | The adverse metabolic effects of prescribed and endogenous glucocorticoid (GC) excess, Cushing syndrome, create a significant health burden. We found that tissue regeneration of GCs by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), rather than circulating delivery, is critical to developing the phenotype of GC excess; 11beta-HSD1 KO mice with circulating GC excess are protected from the glucose intolerance, hyperinsulinemia, hepatic steatosis, adiposity, hypertension, myopathy, and dermal atrophy of Cushing syndrome. Whereas liver-specific 11beta-HSD1 KO mice developed a full Cushingoid phenotype, adipose-specific 11beta-HSD1 KO mice were protected from hepatic steatosis and circulating fatty acid excess. These data challenge our current view of GC action, demonstrating 11beta-HSD1, particularly in adipose tissue, is key to the development of the adverse metabolic profile associated with circulating GC excess, offering 11beta-HSD1 inhibition as a previously unidentified approach to treat Cushing syndrome. |
