Expression of insulin growth factor-1 splice variants and structural genesin rabbit skeletal muscle induced by stretch and stimulation

1. Skeletal muscle is a major source of circulating insulin growth factor-1 (IGF-1), particularly during exercise. It expresses two main isoforms. One of the muscle IGF-1 isoforms (muscle L.IGF-1) is similar to the main liver IGF-1 and presumably has an endocrine action. The other muscle isoform as a result of alternative splicing has a different 3' exon sequence and is ap parently designed for an autocrine/paracrine action (mechano-growth factor, MGF). Using RNase protection assays with a probe that distinguishes these differently spliced forms of IGF-1, their expression and also the expressio n of two structural genes was measured in rabbit extensor digitorum longus muscles subjected to different mechanical signals. 2. Within 4 days, stretch using plaster cast immobilization with the limb i n the plantar flexed position resulted in marked upregulation of both forms of IGF-1 mRNA. Electrical stimulation at 10 Hz combined with stretch (over load) resulted in an even greater increase of both types of IGF-1 transcrip t, whereas electrical stimulation alone, i.e. without stretch, resulted in no significant increase over muscle from sham-operated controls. Previously it was shown that stretch combined with electrical stimulation of the dors iflexor muscles in the adult rabbit results in a marked increase in muscle mass involving increases in both length and girth, within a few days. The e xpression of both systemic and autocrine IGF-1 growth factors provides a li nk between the mechanical signal and the marked increase in the structural gene expression involved in tissue remodelling and repair. 3. The expression of the beta actin gene was seen to be markedly upregulate d in the stretched and stretched/stimulated muscles. It was concluded that the increased expression of this cytoskeletal protein gene is an indication that the production of IGF-1 may initially be a response to local damage. 4. Switches in muscle fibre phenotype were studied using a specific gene pr obe for the 2X myosin heavy chain gene. Type 2X expression was found to dec rease markedly with stimulation alone and when electrical stimulation was c ombined with stretch. Unlike the induction of IGF-1 and beta actin, the dec reased expression of the 2X myosin mRNA was less marked in the 'stretch onl y' muscles. This indicates that the interconversion of fibre type 2X to 2A may in some situations be commensurate with, but not under the control of I GF-1.