Schakman O, Gilson H, Kalista S, Thissen J P
Unité de Diabétologie et Nutrition, Université Catholique de Louvain, Brussels, Belgium.
Horm Res. 2009 Nov;72 Suppl 1:36-41. doi: 10.1159/000229762. Epub 2009 Nov 27.
Many pathological states characterized by muscle atrophy (e.g., 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.
Recent progress in understanding the role of growth factors in GC-induced muscle atrophy allows investigation into new therapies to minimize this myopathy.
许多以肌肉萎缩为特征的病理状态（如败血症、恶病质、饥饿、代谢性酸中毒和严重胰岛素缺乏症）都与循环糖皮质激素（GC）水平升高有关，这表明GC可能引发这些情况下出现的肌肉萎缩。GC诱导的肌肉萎缩是由蛋白质合成减少和蛋白质降解增加导致的。GC对蛋白质合成的抑制作用被认为主要是由于对p70核糖体S6蛋白激酶的抑制。GC对肌肉蛋白水解的刺激作用是由两个主要的细胞蛋白水解系统激活所致：泛素蛋白酶体和溶酶体系统。胰岛素样生长因子I（IGF-I）是一种肌肉合成代谢生长因子，其在肌肉中的产生减少可能导致GC诱导的肌肉萎缩。通过激活磷脂酰肌醇-3-激酶/蛋白激酶B（Akt）途径，IGF-I可抵消GC对肌肉萎缩的抑制作用。有证据还表明，分解代谢生长因子肌生长抑制素的产生增加可能在GC诱导的肌肉萎缩中起关键作用。
在了解生长因子在GC诱导的肌肉萎缩中的作用方面的最新进展使得对新疗法的研究成为可能，以尽量减少这种肌病。
