Open AccessEvaluation of early biomarkers of muscle anabolic response to testosterone
Author(s) -
Chen Fabian,
Lam Raymond,
Shaywitz David,
Hendrickson Ronald C.,
Opiteck Gregory J.,
Wishengrad Dana,
Liaw Andy,
Song Qinghua,
Stewart Adrian J.,
Cummings Corinne E.,
Beals Chan,
Yarasheski Kevin E.,
Reicin Alise,
Ruddy Marcella,
Hu Xuguang,
Yates Nathan A.,
Menetski Joseph,
Herman Gary A.
Publication year - 2011
Publication title -
journal of cachexia, sarcopenia and muscle
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.803
H-Index - 66
eISSN - 2190-6009
pISSN - 2190-5991
DOI - 10.1007/s13539-011-0021-y
Subject(s) - anabolism , testosterone (patch) , anabolic agents , medicine , endocrinology
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.