11β-HSD1 is the major regulator of the tissue-specific effects of circulating glucocorticoid excess.

[cushing syndrome]

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 11 β-hydroxysteroid dehydrogenase type 1 (11 β-HSD 1 ), rather than circulating delivery , is critical to developing the phenotype of GC excess ; 11 β-HSD 1 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 11 β-HSD 1 KO mice developed a full Cushingoid phenotype , adipose-specific 11 β-HSD 1 KO mice were protected from hepatic steatosis and circulating fatty acid excess . These data challenge our current view of GC action , demonstrating 11 β-HSD 1 , particularly in adipose tissue , is key to the development of the adverse metabolic profile associated with circulating GC excess , offering 11 β-HSD 1 inhibition as a previously unidentified approach to treat Cushing syndrome .

Diseases
Validation

Diseases presenting "myopathy" symptom

coats disease

cushing syndrome

dystrophic epidermolysis bullosa

epidermolysis bullosa simplex

familial mediterranean fever

focal myositis

homocystinuria without methylmalonic aciduria

inclusion body myositis

junctional epidermolysis bullosa

lymphangioleiomyomatosis

megacystis-microcolon-intestinal hypoperistalsis syndrome

pyruvate dehydrogenase deficiency

This symptom has already been validated