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Title: Regulation of muscle fibre phenotype, muscle mass and IGF-1 gene expression in skeletal muscle in response to mechanical activity
Author: Yang, Shiyu
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1997
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This thesis is concerned with the regulation of muscle mass, muscle fibre phenotype and the role of IGF-1 expression in skeletal muscle in response to mechanical activity. Initially this work was done by Northern hybridization and then by in situ hybridization. The latter indicated that the end of normal adult fibres is the region of the longitudinal growth and that IGF-1 is involved in this process. By combining in situ hybridization and immunohistochemistry procedures, the effects of passive stretch and disuse of muscle on the expression of IGF-1 mRNA at the individual muscle fibre level and the fibre type composition of the muscles were studied. The result indicated that stretch also induced an increase in the percentage of fibres expressing neonatal and slow myosin and that IGF-1 is involved not only in muscle hypertrophy, but also in muscle fibre conversion. Using RT-PCR a single IGF-1 isoform cDNA (IGF- 1Ea) could be cloned from the normal resting muscles. However, an additional isoform of IGF-1 (IGF-1Eb) was found to be expressed in stretched muscle undergoing hypertrophy. The latter IGF-1 mRNA probably encodes the precursor IGF-1 isoform that is responsible for local muscle growth regulation in response to mechanical signals. To confirm that alternative splicing of the IGF-1 gene occurs in muscle in response to physical activity, oligonucleotide primers were made which specially amplify the cDNAs of two isoforms (IGF-1 Ea and Eb) in the human as well as the rabbit. Following altered physical activity for 2 hours to 6 days, appreciable levels of IGF-1 Eb (in human the Ec) isoform were detected in skeletal muscle by using RT-PCR and RNA protection. These data suggest that the IGF-1 Eb be a link of mechanical activity and the expression of muscle genes in adaptive hypertrophy and repair processes.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available