IGF-I isoforms and ageing skeletal muscle: an 'unresponsive' hypertrophy agent?
IGF-I isoforms and ageing skeletal muscle: an 'unresponsive' hypertrophy agent?
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IGF-I 同工型和衰老骨骼肌：一种“无反应”的肥大剂？
DOI：
10.1113/jphysiol.2002.033738
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Spangenburg,EspenE
中科院分区：
文献类型：
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作者：
Spangenburg,EspenE
肌肉生物学家已经认识到生长因子诱导成年哺乳动物骨骼肌肥大的能力。虽然，这些生长因子诱导骨骼肌肥大的分子机制尚不清楚，但生长因子促进肌肉生长的证据是显而易见的。与肥大过程有关的一种生长因子是胰岛素样生长因子(IGF-I)。IGF-I是一个受多个启动子调控的复杂基因，能够产生至少四种不同的成熟IGF-I前体蛋白(即异构体)。与肥大最相关的两种异构体是：IGF-IEA(称为肌肉IGF-I)，它类似于肝脏产生的IGF-I，以及IGF-IEB(称为机械生长因子)，它似乎只由受损或负荷的骨骼肌产生(Hameed等人)。2003年，发表在本期《生理学杂志》上)。尽管这些不同的IGF-I亚型在肌肉肥大中的作用机制复杂且还不清楚，但这些IGF-I的这些形式是骨骼肌肥大的一个组成部分。骨骼肌IGF-I的mRNA和蛋白表达在机械负荷的早期阶段增加(Adams&Haddad，1996)，这表明肝脏不是IGF-I的唯一来源。随着动物的成熟，生长激素的产生减少，随后肝脏释放的循环IGF-I减少。由于成年哺乳动物保留了增加肌肉质量的能力，因此全身IGF-I的增加不太可能是骨骼肌肥大所必需的，而是依赖于IGF-I的旁分泌/自分泌产生。例如，去垂体的大鼠保留了增加肌肉质量的能力，以应对增加的机械负荷(Goldberg，1967)。然而，无论IGF-I的形式或来源如何，最近Fernández等人(2002)强调了骨骼肌对IGF-I的反应能力，因为含有显性负IGF-I受体的转基因小鼠缺乏增加肌肉质量的能力。
Muscle biologists have recognized the ability of growth factors to induce skeletal muscle hypertrophy in adult mammals. Although, the molecular mechanisms by which these growth factors induce skeletal muscle hypertrophy remain unclear, the evidence that growth factors increase muscle growth is obvious. One growth factor implicated in the hypertrophy process is insulin-like growth factor (IGF-I). IGF-I is a complex gene that is regulated by multiple promoters and is capable of producing at least four different mature IGF-I precursor proteins (ie isoforms). The two isoforms which appear most relevant to hypertrophy are: IGF-IEa (termed muscle IGF-I), which is similar to the IGF-I produced by the liver, and IGF-IEb (termed mechano-growth factor), which only appears to be produced by damaged or loaded skeletal muscle (Hameed et al. 2003, published in this issue of The Journal of Physiology). Although, the mechanistic roles of these different isoforms of IGF-I in muscle hypertrophy are complex and not well understood, these forms of IGF-I are an integral component of skeletal muscle hypertrophy.Skeletal muscle IGF-I mRNA and protein expression increase during the early phases of mechanical loading (Adams & Haddad, 1996), indicating that the liver is not the only source of IGF-I. As the animal matures, there is decreased production of growth hormone and subsequently a decline in circulating IGF-I released by the liver. Since adult mammals retain the ability to increase muscle mass it is unlikely that increases in systemic IGF-I are necessary for skeletal muscle hypertrophy and instead rely on paracrine/autocrine production of IGF-I. For example, hypophysectomized rats retain the ability to increase muscle mass in response to increased mechanical loading (Goldberg, 1967). However, the ability of skeletal muscle to respond to IGF-I regardless of the form or source of IGF-I was recently emphasized by Fernández et al.(2002), in that transgenic mice containing a dominant negative IGF-I receptor lacked the ability to increase muscle mass.