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Androgen receptor polyglutamine repeat length affects receptor activity and C2C12 cell development.
Ryan L Sheppard1, Espen E Spangenburg, Eva R Chin
1Department of Kinesiology, School of Public Health, University of Maryland, College Park, Maryland 20742, USA.
Physiological Genomics
|August 11, 2011
Summary
The androgen receptor (AR) polyglutamine repeat length influences skeletal muscle cell growth and development. Longer AR CAG repeats increase AR transcriptional activity but decrease C2C12 cell proliferation and myonuclear fusion.
Area of Science:
- Molecular Biology
- Cell Biology
- Genetics
Background:
- Testosterone (T) exerts anabolic effects on skeletal muscle, primarily through the androgen receptor (AR).
- The AR gene contains a polymorphic CAG repeat region, influencing receptor activity in other tissues.
- The impact of AR CAG repeat length on skeletal muscle function remains largely unknown.
Purpose of the Study:
- To investigate the effect of AR CAG repeat length on AR function in C2C12 skeletal muscle cells.
- To determine how varying AR polyglutamine repeat lengths impact cellular processes like proliferation, differentiation, and gene expression.
Main Methods:
- Utilized C2C12 cells stably transfected with AR expression vectors containing 14, 24, or 33 CAG repeats.
- Assessed AR transcriptional activity, ligand activation, mRNA expression, cell proliferation, and creatine kinase (CK) activity.
- Evaluated myotube formation, myonuclear fusion index, and expression of myostatin and myogenin via RT-PCR.
Main Results:
- AR transcriptional activity and ligand activation significantly increased with longer CAG repeat lengths.
- AR mRNA expression was elevated in all stably transfected lines.
- Cell proliferation decreased with longer repeat lengths, while CK activity was higher in AR33 cells compared to AR14.
- Myonuclear fusion index was reduced in AR14 and AR33 cells, with atypical myotube morphology observed. Genotype differences in myostatin and myogenin expression were detected.
Conclusions:
- AR polyglutamine repeat length is directly associated with AR transcriptional activity in skeletal muscle cells.
- This polymorphism significantly alters C2C12 cell growth, differentiation, and myotube development.
- The AR CAG repeat length may be a heritable factor influencing human skeletal muscle mass.
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