Endocrine Abstracts (2007) 13 OC21

Muscle cell differentiation is regulated by glucocorticoids, a process which is potentiated through the induction of 11 beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1)

Mark Sherlock, Gareth Lavery, Jenny Horsburgh, Ana Slabbert, Andy Toogood & Paul Stewart

University of Birmingham, Birmingham, United Kingdom.

In vivo the 11β-HSD1 enzyme converts inactive cortisone to the active glucocorticoid cortisol. 11β-HSD1 is implicated in the metabolic syndrome through its expression in liver and adipose tissue by increasing local cortisol concentrations. However, little is known regarding the expression and function of 11β-HSD1 in muscle.

Murine C2C12 muscle cells (myocytes) were differentiated from myoblasts to myotubules for 8 days, with and without the glucocorticoid receptor (GR) antagonist RU486. During this process 11β-HSD1 expression and activity, and the expression of the myocyte differentiation markers α-actin and myogenin were measured.

11β-HSD1 mRNA expression increased 38-fold during differentiation from myoblasts to myotubules (P<0.01) with an increase in 11β-HSD1 oxoreductase activity from 1.2(+0.2) to 20.7(+2.32) pmol conversion/mg protein/hour (P<0.001). α-actin and myogenin (myocyte differentiation markers) increased significantly between myoblasts and myotubules with a 32-fold increase in expression of α-actin (P<0.001) and an 8-fold increase in myogenin mRNA expression (P=0.03) between myoblasts and myotubules. Addition of the GR-antagonist RU486 resulted in a 50-fold decrease in expression of α-actin mRNA (P=0.002) and >300-fold decrease in myogenin (P<0.001) compared to untreated myotubules.

Skeletal muscle is a metabolically active tissue that is responsive to glucocorticoids. We have shown high 11β-HSD1 expression and activity within muscle which may be important in regulating local glucocorticoid mediated effects on myotubule differentiation. Antagonism of the GR results in decreased expression of myocyte differentiation markers. The high expression and activity of 11β-HSD1 in muscle highlights the potential importance of 11β-HSD1 in the aetiology of the metabolic syndrome and the myopathy associated with glucocorticoid deficiency and excess.

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