Androgens increase muscle size through the androgen receptor (AR), which rapidly activates signalling pathways to trigger various biological responses. Rapid androgen effects occur through interaction of AR with effectors or scaffolds, including the Src tyrosine-kinase and filamin A. Activation of the downstream effectors (paxillin, FAK, MAPK, Akt) then follows. Ageing is often accompanied by the loss of skeletal muscle mass, likely caused by derangements of hormonal responses. By using human skeletal muscle biopsies, we have analysed the key molecules linking the AR nongenomic axis with cytoskeleton organization. Proteins from young or old women (3 for each group) biopsies have been analyzed by Western blot, using appropriate antibodies (anti-phosphofilamin A and filamin A; antiphosphopaxillin and paxillin). Proteins have been also analysed for AR and estrogen receptor alpha (ERα) expression levels. Representative blots from each subset of participants are presented in Figure. Phosphorylation of both Ser-2152 filamin A and Tyr-118 paxillin (A) is stronger in biopsies from old women, as compared with that obtained from young women. Conversely, the expression of AR and ERα (B) is weaker in samples from old women, as compared with that obtained from young women. Proteins from control breast cancer-derived MCF-7 cells are analysed in parallel (ctrl). Our study suggests that derangement of the AR axis occurs in skeletal muscle from old women. This event likely leads to excessive metabolic functions and loss of skeletal muscle. Further investigation in cultured cells and mouse models might help us in targeting the skeletal muscle AR axis with new compounds (new selective androgen receptor modulators or stapled-peptides; 1 and 2) to improve the clinical outcome of age-related diseases. 1) Migliaccio et al., Oncogene 2007;26:6619. 2) Castoria et al., Cell Death Dis 2014;5:e1548.
|Titolo:||P491 THE ANDROGEN RECEPTOR IN HUMAN SKELETAL MUSCLE BIOPSIES|
|Data di pubblicazione:||2015|
|Appare nelle tipologie:||1.5 Abstract in rivista|