A loss of muscle mass, or atrophy, is known to occur during prolonged exposure to a micro gravitational environment and this is one of the main problems facing humans during prolonged space flight. In contrast, muscles will increase in size, or hypertrophy, when mechanically overloaded. The mechanisms regulating these processes are still not fully understood, yet it is clear that mechanical signals in some way play an integral part in regulating muscle mass. Insulin like growth factor-I (IGF-I) is known to have a number of important physiological roles and it is known that one of these is an anabolic function in skeletal muscle. In addition to the production of IGF-I from the liver, it is now well established that other tissues can produce IGF-I for autocrine and/or paracrine actions. We have recently confirmed the results of earlier animal studies (Yang et al. Mus. Res. Cell. Mot. 1996:17:487-496) that human skeletal muscles express the mRNA of at least two isoforms of IGF-I (Hameed et al. J.Physiol 2002 Abstract in press). The first, termed IGF-IEa, which is similar to the systemic or liver type and a second, which is apparently upregulated in response to mechanical signals and to damage. This isoform has been termed mechano growth factor, or MGF and results from alternative splicing of the IGF-I gene. It differs from the IGF-IEa isoform in humans by having the first 49 base pairs of exon 5. This alters the reading frame of the C terminus thereby resulting in a different E peptide. We have shown that in young subjects there is an upregulation of MGF mRNA 2½ hours after a single bout of high load resistance exercise. In contrast, no change was seen in the mRNA levels of the IGF-IEa isoform. In rat muscle it has been shown that the IGF-I gene is first spliced to MGF expression and then to the IGF-IEa isoform (Owino et al. FEBS Lett 2001; 505:259-63, Hill and Goldspink unpublished). This suggests a differential regulation of the two isoforms. The mechano-transduction pathways that may be involved in regulating MGF are not known, but interestingly dystrophic (mdx) mice that lack the important structural protein dystophin, do not express MGF after mechanical overload (Goldspink et al. J Physiol 1996: 495P:162P-163P). Although, MGF is expressed at lower levels than the IGF-IEa isoform, this growth factor appears to be extremely potent. For example, when the cDNA of MGF was injected into the muscles of mice, the muscles were stimulated to grow rapidly resulting in a ~25% increase in muscle mass in 2 weeks Goldspink 2001, US Patent 09/142,583). Recent studies on C2/C12 cells in culture have shown that a different response is evoked depending upon whether they have been treated with either MGF or IGF-IEa peptides. MGF results in a proliferation of cells remaining in the mononucleated state, whilst IGF-1Ea treated cells differentiate into myotubes (Yang & Goldspink. FEBS Lett. 2002;522:156-60). It is thus likely that MGF works not only through increasing protein synthesis through the IGF-1 signalling pathways, but also through the activation of satellite cells which provide the additional nuclei required for muscle fibre hypertrophy.

Unfortunately data from this presentation is awaiting publication, and is therefore not avaliable at the present time.

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