11ß-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, 2014 Jun 17.
Article
em En
| MEDLINE
| ID: mdl-24889609
ABSTRACT
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 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1), rather than circulating delivery, is critical to developing the phenotype of GC excess; 11ß-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 11ß-HSD1 KO mice developed a full Cushingoid phenotype, adipose-specific 11ß-HSD1 KO mice were protected from hepatic steatosis and circulating fatty acid excess. These data challenge our current view of GC action, demonstrating 11ß-HSD1, particularly in adipose tissue, is key to the development of the adverse metabolic profile associated with circulating GC excess, offering 11ß-HSD1 inhibition as a previously unidentified approach to treat Cushing syndrome.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Hidrocortisona
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Tecido Adiposo
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Síndrome de Cushing
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11-beta-Hidroxiesteroide Desidrogenase Tipo 1
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Glucocorticoides
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article