期刊
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
卷 2, 期 1, 页码 45-56出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s13539-011-0021-y
关键词
RNA microarray profiling; Proteomics; Testosterone; Mass spectrometry; Sarcopenia; Frailty
资金
- Merck Co. Inc.
Background Early biomarkers of skeletal muscle anabolism will facilitate the development of therapies for sarcopenia and frailty. Methods and results We examined plasma type III collagen N-terminal propeptide (P3NP), skeletal muscle protein fractional synthesis rate, and gene and protein expression profiles to identify testosterone-induced changes in muscle anabolism. Two placebo-controlled studies enrolled community-dwelling men (study 1, 60-75 years; study 2, 18-40 years) with low to normal testosterone levels. Men were randomized to lower dose (study 1, 100 mg; study 2, 200 mg) or higher dose (study 1, 300 mg; study 2, 600 mg) single intramuscular testosterone or saline injection. After 1 week, testosterone acutely increased plasma P3NP levels in a dose-dependent manner and altered the expression of several skeletal muscle transcripts and proteins. Though not statistically significant, mixed muscle protein fractional synthesis rate tended to increase (1.08-fold with 100 mg testosterone, 1.12-fold with 300 mg testosterone). Testosterone exposure also increased skeletal muscle expression of the collagen type III gene that encodes P3NP. Conclusion P3NP is a potentially useful early biomarker for muscle anabolic therapy. Skeletal muscle protein and RNA profiling are useful tools for the discovery of novel muscle anabolic biomarkers.
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