Mechanisms of muscle atrophy induced by glucocorticoids

O Schakman, H Gilson, S Kalista, JP Thissen - Hormone research, 2009 - karger.com
O Schakman, H Gilson, S Kalista, JP Thissen
Hormone research, 2009karger.com
Background: Many pathological states characterized by muscle atrophy (eg, sepsis,
cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an
increase in circulating glucocorticoid (GC) levels, suggesting that GC could trigger the
muscle atrophy observed in these conditions. GC-induced muscle atrophy results from
decreased protein synthesis and increased protein degradation. The inhibitory effect of GCs
on protein synthesis is thought to result mainly from the inhibition of the p70 ribosomal S6 …
Abstract
Background: Many pathological states characterized by muscle atrophy (eg, sepsis, cachexia, starvation, metabolic acidosis and severe insulinopenia) are associated with an increase in circulating glucocorticoid (GC) levels, suggesting that GC could trigger the muscle atrophy observed in these conditions. GC-induced muscle atrophy results from decreased protein synthesis and increased protein degradation. The inhibitory effect of GCs on protein synthesis is thought to result mainly from the inhibition of the p70 ribosomal S6 protein kinase. The stimulatory effect of GCs on muscle proteolysis results from the activation of two major cellular proteolytic systems: ubiquitin proteasome and lysosomal systems. The decrease in muscle production of insulin-like growth factor I (IGF-I), a muscle anabolic growth factor, could contribute to GC-induced muscle atrophy. By activating the phosphatidylinositol-3-kinase/Akt pathway, IGF-I overrides GC action to stunt muscle atrophy. Evidence also indicates that increased production of myostatin, a catabolic growth factor, could play a critical role in GC-induced muscle atrophy. Conclusions: Recent progress in understanding the role of growth factors in GC-induced muscle atrophy allows investigation into new therapies to minimize this myopathy.
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