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

Abstract

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) old ( n = 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 = 0.395, P = 0.007) as well as AR and Wnt5 protein levels (r = 0.670, P < 0.001). We next tested the hypothesis that Wnt5 affects muscle fiber size by treating CC-derived myotubes with lower (75 ng/ml) and higher (150 ng/ml) concentrations of recombinant Wnt5a protein. Both treatments increased myotube size ( P < 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 = 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 < 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.

Growth Hormone(s), Testosterone, Insulin-Like Growth Factors, and Cortisol: Roles and Integration for Cellular Development and Growth With Exercise

“…The presence of T increases AR-β-catenin interaction and transcriptional capacity. Positive correlations were shown between AR protein content and Wnt5 expression and muscle mass and Wnt5 expression in rats (44). Testosterone treatment increased Wnt5 protein expression and muscle size in a dosedependent manner (44).…”

“…Positive correlations were shown between AR protein content and Wnt5 expression and muscle mass and Wnt5 expression in rats (44). Testosterone treatment increased Wnt5 protein expression and muscle size in a dosedependent manner (44). Spillane et al (45) reported significant up-regulation of VL muscle β-catenin following upper and lower body RT at 3 and 24 h PE and increased AR-DNA binding capacity and suggested the increased binding capacity was linked to greater β-catenin pathway signaling.…”

The Effects of a Theacrine-based Supplement on mRNAs Related to Various Metabolic Processes and Sirtuin Activity in vitro

“…Cell culture methods were performed similar to other studies published by our laboratory (16,17). Brie y, C2C12 myoblasts (passage 6; American Type Culture Collection, Manassas, VA, USA), were seeded in growth medium (DMEM, 10% FBS, 1% penicillin/streptomycin, and 0.1% gentamycin) on six-well plates at a seeding density of 3 x10 5 under standard culture conditions (37°C in a 5% CO 2 atmosphere).…”

Functions and Regulatory Mechanisms of lncRNAs in Skeletal Myogenesis, Muscle Disease and Meat Production

“…MAR1 also affects myogenesis by enhancing Wnt5a function [54]. Wnt5a may contribute to age-related skeletal muscle atrophy in rats [55]. These studies suggest that MAR1 may be involved in the Wnt5a-regulated muscular atrophy pathway.…”