Odedra B R, Millward D J
Biochem J. 1982 Jun 15;204(3):663-72. doi: 10.1042/bj2040663.
The effect of corticosterone on protein turnover in skeletal muscle was investigated in growing rats. Protein synthesis was measured in vivo by the constant infusion of [(14)C]tyrosine. The extent to which any effect of corticosterone is modulated by the hyperinsulinaemia induced by steroid treatment was examined by giving the hormone not only to adrenalectomized rats but also to streptozotocin-induced diabetic rats maintained throughout the treatment period on two dosages of insulin by an implanted osmotic minipump. Approximate rates of protein degradation were also estimated in some cases as the difference between synthesis and net change in muscle protein mass. Measurements were also made of free 3-methylhistidine concentration in muscle and plasma. At 10mg of corticosterone/100g body wt. per day, growth stopped and muscle wasting occurred, whereas at 5 mg of corticosterone/100g body wt. per day no net loss of protein occurred. However, this low dose did induce muscle wasting when insulin concentration was regulated by a dose of 1.2 units/day. Protein synthesis was markedly depressed in all treated groups, the depression in the insulin-maintained rats being marginally more than in the hyperinsulinaemic adrenalectomized rats. The oxidative soleus muscle appeared to be less susceptible to the effect of the corticosterone than was the more glycolytic plantaris or gastrocnemius muscle. Any effect of the corticosterone on protein degradation was much less than its effects on protein synthesis. Where increases in the degradation rates appeared to occur in the rats treated with 10mg of corticosterone/100g body wt. per day, the increases were less than 20%. The free intracellular 3-methylhistidine concentrations were doubled in all groups treated with 5 mg of corticosterone/100g body wt. per day and increased 5-fold in the adrenalectomized rats treated with 10mg of corticosterone/100g body wt. per day, with no change in plasma concentration in any of the groups. It is therefore concluded that: (a) the suppression of protein synthesis is the main effect of glucocorticoids in muscle; (b) marked increases in insulin afford only minor protection against this effect; (c) stimulation of protein degradation may occur, but to a much lesser extent.
研究了皮质酮对生长中大鼠骨骼肌蛋白质周转的影响。通过持续输注[(14)C]酪氨酸在体内测量蛋白质合成。通过不仅给肾上腺切除的大鼠，而且给链脲佐菌素诱导的糖尿病大鼠注射皮质酮来研究皮质酮的任何作用在类固醇治疗诱导的高胰岛素血症下受到的调节程度，这些糖尿病大鼠在整个治疗期间通过植入的渗透微型泵接受两种剂量的胰岛素。在某些情况下，还通过合成与肌肉蛋白质量净变化之间的差异来估计蛋白质降解的大致速率。还测量了肌肉和血浆中游离3-甲基组氨酸的浓度。每天给予10mg皮质酮/100g体重时，生长停止且出现肌肉萎缩，而每天给予5mg皮质酮/100g体重时未发生蛋白质净损失。然而，当胰岛素浓度通过每天1.2单位的剂量调节时，这个低剂量确实会导致肌肉萎缩。所有治疗组的蛋白质合成均明显受到抑制，胰岛素维持的大鼠中的抑制程度略高于高胰岛素血症的肾上腺切除大鼠。与糖酵解程度更高的跖肌或腓肠肌相比，氧化型比目鱼肌似乎对皮质酮的作用更不敏感。皮质酮对蛋白质降解的任何作用都远小于其对蛋白质合成的作用。在每天给予10mg皮质酮/100g体重的大鼠中，降解速率似乎增加的情况下，增加幅度小于20%。每天给予5mg皮质酮/100g体重的所有组中，细胞内游离3-甲基组氨酸浓度增加了一倍，而每天给予10mg皮质酮/100g体重的肾上腺切除大鼠中增加了5倍，所有组的血浆浓度均无变化。因此得出结论：(a)蛋白质合成的抑制是糖皮质激素在肌肉中的主要作用；(b)显著增加胰岛素对这种作用仅提供轻微保护；(c)可能会发生蛋白质降解的刺激，但程度要小得多。
