Sex-based Differences in Resting MAPK, Androgen, and Glucocorticoid Receptor Phosphorylation in Human Skeletal Muscle

Purpose: To determine if there is differential expression and phosphorylation of the androgen receptor (AR), glucocorticoid receptor (GR), and mitogen-activated protein kinases (MAPK) in skeletal muscle at rest between males and females.

Methods: Ten college-aged males (mean ± SD; age = 22 ± 2.4 yrs, ht = 175 ± 7 cm, body mass = 84.1 ± 11.8 kg) and ten females (mean ± SD; age = 20 ± 0.9 yrs; ht = 169 ± 7 cm; body mass = 67.1 ± 8.7 kg) reported to the laboratory following an overnight fast. Resting muscle biopsies were collected from the vastus lateralis and analyzed for total and phosphorylated GR (ser134, ser211, and ser226), total and phosphorylated AR (ser81, ser213, ser515, ser650), and total and phosphorylated MAPK (ERK, JNK, p38) via western blotting. A phosphorylation index (PI) was calculated to determine phosphorylated receptor expression after accounting for differences in total receptor content.

Results: Males had more total AR compared to females (+42 ± 4%; p < 0.001). Females had higher phosphorylation of ARser81 (+87 ± 11%; p = 0.001) and ser515 (+55 ± 13%; p = 0.019). However, when the phosphorylated ratios were corrected for differences in total AR expression (i.e. our PI), the overall phosphorylation at these sites were similar between sexes (ser515, males = 100% vs females 92%; ser81, males = 100% vs females = 107%). pGRser134 was higher in males compared to females (+50 ± 15%; p = 0.016). Phospho-p38 was higher in females compared to males (+5050 ± 16%; p < 0.001).

Conclusion: At rest, ARs and GRs are differentially phosphorylated at some, but not all sites when comparing males and females. Differential regulation of phosphorylated AR, GR, and p38 between males and females may have implications for the degree of muscle adaptations observed following resistance or endurance training.