Cross talk between androgen and Wnt signaling potentially contributes to age-related skeletal muscle atrophy in rats

Petey W. Mumford, Matthew A. Romero, Xuansong Mao, C. Brooks Mobley, Wesley C. Kephart, Cody T. Haun, Paul A. Roberson, Kaelin C. Young, Jeffrey S. Martin, Joshua F. Yarrow, Darren T. Beck, Michael D. Roberts
2018 Journal of applied physiology  
DT, Roberts MD. Cross talk between androgen and Wnt signaling potentially contributes to age-related skeletal muscle atrophy in rats. We sought to determine whether age-related gastrocnemius muscle mass loss was associated with parallel decrements in androgen receptor (AR) or select Wnt signaling markers. To test this hypothesis, serum-free and total testosterone (TEST) and gastrocnemius AR and Wnt signaling markers were analyzed in male Fischer 344 rats that were 3, 6, 12, 18, and 24 mo (mo)
more » ... 8, and 24 mo (mo) old (n ϭ 9 per group). Free and total TEST was greatest in 6 mo rats, and AR protein and Wnt5 protein levels linearly declined with aging. There were associations between Wnt5 protein levels and relative gastrocnemius mass (r ϭ 0.395, P ϭ 0.007) as well as AR and Wnt5 protein levels (r ϭ 0.670, P Ͻ 0.001). We next tested the hypothesis that Wnt5 affects muscle fiber size by treating C2C12derived myotubes with lower (75 ng/ml) and higher (150 ng/ml) concentrations of recombinant Wnt5a protein. Both treatments increased myotube size (P Ͻ 0.05) suggesting this ligand may affect muscle fiber size in vivo. We next tested if Wnt5a protein levels were androgen-modulated by examining 10-mo-old male Fischer 344 rats (n ϭ 10 -11 per group) that were orchiectomized and treated with testosterone-enanthate (TEST-E); trenbolone enanthate (TREN), a nonaromatizable synthetic testosterone analogue; or a vehicle (ORX only) for 4 wk. Interestingly, TEST-E and TREN treatments increased Wnt5a protein in the androgen-sensitive levator ani/bulbocavernosus muscle compared with ORX only (P Ͻ 0.05). To summarize, aromatizable and nonaromatizable androgens increase Wnt5a protein expression in skeletal muscle, age-related decrements in muscle AR may contribute Wnt5a protein decrements, and our in vitro data imply this mechanism may contribute to age-related muscle loss. NEW & NOTEWORTHY Results from this study demonstrate androgen and Wnt5 protein expression decrease with aging, and this may be a mechanism involved with age-related muscle loss.
doi:10.1152/japplphysiol.00768.2017 pmid:29722624 fatcat:5cjhkmy47nhuhgvhsvt4yjfkfy