Expression of myogenic regulatory factors in normal and dystrophic mice: effects of IGF-1 treatment.
Myogenic regulatory factors (MRFs) promote differentiation of muscle cells from fibroblasts and are induced by insulin-like growth factor I (IGF-1). Prior studies have shown synthesis of new muscle protein and improved muscle morphology when mature dy mice with muscular dystrophy are treated with IGF-1. We investigated whether these salutary effects of IGF-1 might be attributable to stimulation of MRFs. Male dy (129ReJ) mice and controls (129J) were assigned to IGF-1 treatment (10 micrograms twice daily) or non-treatment at about 5 weeks of life and sacrificed 6 weeks later. RNA was extracted from skeletal muscles, reverse transcribed, and amplified by polymerase chain reaction (PCR) using primers specific for each MRF. Competitive PCR was performed to quantify MyoD expression in response to IGF-1 treatment. Transcripts for myf-5, MRF4, and myogenin were detected in both control and dy mouse muscles; no apparent differences were observed between treatment groups. Quantitative analysis of transcripts for MyoD indicated no significant basal differences between control and dy mice. There was, however, significantly higher MyoD expression in the dy group, and a trend toward significance in the control group, following IGF-1 treatment. These data suggest that IGF-1 exerts its in vivo effects in postembryonal muscle by stimulating MRFs.
Hsu
H H
HH
Department of Pediatrics, North Shore University Hospital-New York University School of Medicine, Manhasset 11030, USA.
Zdanowicz
M M
MM
Agarwal
V R
VR
Speiser
P W
PW
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins; D015870:Gene Expression / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009124:Muscle Proteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D017570:MyoD Protein / Q000235:genetics; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors / Q000235:genetics*; D018008:Myogenin / Q000235:genetics; D015534:Trans-Activators
D017931:DNA Primers; D004268:DNA-Binding Proteins; D009124:Muscle Proteins; C497418:Myf5 protein, mouse; D017570:MyoD Protein; C503801:Myog protein, mouse; D051787:Myogenic Regulatory Factor 5; D018006:Myogenic Regulatory Factors; D018008:Myogenin; D015534:Trans-Activators; C063403:myogenic factor 6; D007334:Insulin-Like Growth Factor I; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases