Hosoyama Tohru, Tachi Chikashi, Yamanouchi Keitaro, Nishihara Masugi
Department of Biology, Faculty of Science, Graduate School of Science and Technology, Chiba University, Japan.
Zoolog Sci. 2005 Feb;22(2):229-36. doi: 10.2108/zsj.22.229.
Skeletal muscle wasting is a common symptom in the adrenal insufficiency such as Addison's disease. Although it has been suspected that several cytokines and/or growth factors are responsible for the manifestation of the symptom, the precise mechanisms underlying the phenomenon have so far been poorly understood. Myostatin is predominantly expressed in skeletal muscles and involved in the regulation of skeletal muscle mass. Recently, several reports indicated that myostatin is secreted into the circulation and the increased levels of circulating myostatin is associated with the induction of skeletal muscle wasting in adult animals. We, therefore, hypothesized that the increased levels of circulating myostatin may account for the development of skeletal muscle wasting in adrenal insufficiency. To test the validity of this hypothesis, we compared the serum levels of myostatin in normal with those in bilaterally adrenalectomized (ADX) rats, a model of Addison's disease, by Western blot analysis. The active form of myostatin (13 kDa) was barely detectable in the sera collected either 1 month or 2 month after adrenalectomy, but present at conspicuously detectable levels in those obtained 3 month after the operation, while the total amounts of myostatin proteins (sum of the precursor and the active forms) remained constant at all the time points examined post-operatively. These results are consistent with the hypothesis that the increased serum levels of active form of myostatin protein, induced yet unknown post-translational control mechanisms may be responsible, at least in part, for the muscle wasting associated with the adrenal insufficiency syndromes.
骨骼肌萎缩是肾上腺皮质功能不全（如艾迪生病）的常见症状。尽管人们怀疑几种细胞因子和/或生长因子是导致该症状的原因，但迄今为止，对这一现象背后的确切机制仍知之甚少。肌肉生长抑制素主要在骨骼肌中表达，并参与骨骼肌质量的调节。最近，有几份报告表明，肌肉生长抑制素会分泌到循环系统中，循环中肌肉生长抑制素水平的升高与成年动物骨骼肌萎缩的发生有关。因此，我们推测循环中肌肉生长抑制素水平的升高可能是肾上腺皮质功能不全时骨骼肌萎缩发展的原因。为了验证这一假设的正确性，我们通过蛋白质免疫印迹分析比较了正常大鼠和双侧肾上腺切除（ADX）大鼠（一种艾迪生病模型）血清中肌肉生长抑制素的水平。肾上腺切除术后1个月或2个月采集的血清中几乎检测不到肌肉生长抑制素的活性形式（13 kDa），但在术后3个月采集的血清中其水平明显可检测到，而在术后所有检测时间点，肌肉生长抑制素蛋白的总量（前体和活性形式的总和）保持恒定。这些结果与以下假设一致，即肌肉生长抑制素蛋白活性形式的血清水平升高，可能是由尚未知的翻译后调控机制诱导的，这至少在一定程度上导致了与肾上腺皮质功能不全综合征相关的肌肉萎缩。
