The Relationship Between Serum Testosterone And Skeletal Muscle Wnt Signaling Markers In 3-24-month Old Rats

Abstract

PURPOSE: We sought to determine if canonical Wnt signaling markers are related to serum testosterone concentrations and muscle weights in rodents. METHODS: Male Fischer 344 rats (300-600g) were aged 3, 6, 12, 18 and 24 months, euthanized, gastrocnemius muscle was extracted and wet skeletal muscle weights were obtained. Muscle tissue was then processed for analysis via western blotting. Additionally, serum was obtained and assays were performed for total and free testosterone (TEST). RESULTS: Relative (body mass-adjusted) gastrocnemius masses revealed significant between-group differences (p<0.001) and were greater at 3 and 6 versus 12, 18 and 24 months (p<0.05). Serum free TEST was 102% greater at 6 versus 3 (p<0.05), 165% greater at 6 versus 12 (p<0.05), 101% greater at 6 versus 18 (p<0.05), and 95% greater at 6 versus 24 months (p<0.05).Total TEST was 305% greater at 6 versus 12 (p<0.05), 273% greater at 6 versus 18 (p<0.05), and 185% greater at 6 versus 24 months (p<0.05). Wnt5a/b was 26% greater at 3 versus 12 (p<0.05), and 54% at 3 versus 24 months (p<0.05). Additionally, Wnt5a/b was 26% greater at 6 versus 12 (p<0.05), and 54% at 6 versus greater than 24 months (p<0.05). Relative gastrocnemius masses and Wnt5a/b exhibited a moderate positive correlation r=0.397, (p=0.007). Beta-catenin was greater at 6 versus 3 and 18 months (p<0.05). Additionally, beta-catenin was greater at 12 versus 3 and 18 months (p<0.05), and 24 versus 3 and 18 months (p<0.05). Androgen receptor (AR) was greater at 3 versus 18 and 24 months (p<0.05), greater at 6 versus 18 and 24 months, and greater at 12 versus 18 and 24 months (p<0.05). Furthermore, AR had a moderate positive correlation r=0.438, (p=0.003) with relative gastrocnemius masses. Additionally, AR had a strong positive relationship correlation r=0.670, (p<0.001) with Wnt5a/b. CONCLUSIONS: It appears that intramuscular Wnt signaling proteins, androgen receptor content, serum testosterone, and gastrocnemius masses are inter-related, and decline with aging. Androgen-sensitive mechanisms related to Wnt signaling should be further investigated in skeletal muscle in order to ascertain if these processes contribute to sacropenia.