Hosoyama Tohru, Yamanouchi Keitaro, Nishihara Masugi
Department of Veterinary Physiology, Veterinary Medical Science, The University of Tokyo, Japan.
J Reprod Dev. 2006 Aug;52(4):469-78. doi: 10.1262/jrd.18009. Epub 2006 Mar 31.
Myostatin, also known as GDF-8 (Growth/Differentiation Factor-8), is a member of the TGF-beta superfamily that negatively regulates skeletal muscle mass in mammals. Mutation of the myostatin gene in mice, cattle, and humans causes a massively developed skeletal muscle, characterized by muscle hypertrophy and hyperplasia. Although myostatin is predominantly expressed in skeletal muscle tissue, several recent studies have shown the presence of myostatin protein in blood and suggested a possible role for circulating myostatin in the regulation of skeletal muscle mass. In the present study, we examined changes in the levels of active form myostatin (13 kDa) in serum after birth by Western blot analysis to predict the role of serum myostatin in early postnatal muscle growth in the rat. Interestingly, the amount of active form myostatin in serum increased after birth and then decreased along with ageing after weaning. To clarify the role of increased serum myostatin during the postnatal period, we administrated follistatin, an inhibitor of myostatin activity, into postnatal rats intraperitoneally just after birth. Follistatin-administration during the postnatal period caused selective hypertrophy of type II muscle fibers in the soleus muscle. These results demonstrate that myostatin in serum acts on skeletal muscle and negatively regulates early postnatal muscle growth.
肌肉生长抑制素,也被称为生长分化因子8(GDF - 8),是转化生长因子β(TGF - β)超家族的成员之一,在哺乳动物中对骨骼肌质量起负调控作用。小鼠、牛和人类的肌肉生长抑制素基因突变会导致骨骼肌大量发育,其特征为肌肉肥大和增生。尽管肌肉生长抑制素主要在骨骼肌组织中表达,但最近的几项研究表明血液中存在肌肉生长抑制素蛋白,并提示循环中的肌肉生长抑制素在调节骨骼肌质量方面可能发挥作用。在本研究中,我们通过蛋白质免疫印迹分析检测出生后血清中活性形式的肌肉生长抑制素(13 kDa)水平的变化,以预测血清肌肉生长抑制素在大鼠出生后早期肌肉生长中的作用。有趣的是,血清中活性形式的肌肉生长抑制素含量在出生后增加,然后在断奶后随着年龄增长而下降。为了阐明出生后血清中肌肉生长抑制素增加的作用,我们在出生后立即给新生大鼠腹腔注射肌肉生长抑制素活性抑制剂卵泡抑素。出生后时期给予卵泡抑素导致比目鱼肌中II型肌纤维选择性肥大。这些结果表明,血清中的肌肉生长抑制素作用于骨骼肌,并对出生后早期肌肉生长起负调控作用。