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Title: The role of IGF-l in the anabolic effects of androgens on skeletal muscle
Author: Solomon, Andrew Martin
ISNI:       0000 0004 2726 4073
Awarding Body: Oxford University
Current Institution: University of Oxford
Date of Award: 2010
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The mechanism whereby anabolic androgens affect the myogenic development of skeletal muscle is incompletely understood. Three different forms of assessing elements of this process were utlilised. Firstly, experiments were designed to test whether androgens had any effect on the proliferation and differentiation of C2C 12 cells; then assessment of changes in gene expression after a specified time in differentiation medium was made. Secondly, the effect on androgens on gene expression in differentiating human primary cultured cells was tested has not been reported previously. The third type of study involved a system that used microarray technology to consider whether a candidate gene could be indentified that may be associated with a clinical condition of unexplained spontaneous muscle hypertrophy. Objectives: 1) To assess effects of androgen +1- IGF-l on expression of IGF-l mRNA in muscle-derived precursor cells. 2) To identify potential candidate genes involved in excessive muscle hypertrophy in an adult male subject. Methods:C2C12 or human muscle-derived cells were differentiated in the presence of androgen (testosterone, T, 0-500nM or dihydrotestosterone, DHT, 0-300nM) and/or IGF -1 (10-50ng/ml). Immunostaining and RT -PCR were used to assess the effect of androgens and IGF -l on muscle-specific proteins and the dynamics of relevant gene expression respectively. A microarray methodology was employed to assess the skeletal muscle gene expression of clinical subjects with spontaneous muscle hypertrophy. Results: Significantly increased myogenicity occurred in human muscle-derived cells exposed to IGF-l (p
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available