PROTECTIVE ROLE OF 17 beta-ESTRADIOL AND TESTOSTERONE IN APOPTOSIS OF SKELETAL MUSCLE

The loss of muscle mass and strength with aging, also referred to as sarcopenia, is a prevalent condition among the elderly and predicts adverse outcomes, including disability, institutionalization and mortality. Sarcopenia has been associated to a deficit of sex hormones since the levels of estrogens and/or testosterone decline upon ageing. Although the mechanisms underlying sarcopenia are far from being clarified, evidence suggests that an age-related acceleration of myocyte loss via apoptosis might represent a mechanism responsible for muscle loss performance. Furthermore, increased levels of apoptosis have also been reported in old rats undergoing muscle atrophy. We previously demonstrated that 17 beta-estradiol (E2) inhibits apoptosis in C2C12 murine skeletal muscle cells through estrogen receptors (ERs) with non classical localization involving PI3K/Akt, MAPKs and HSP27. Here, using siRNAs to silence ER isoforms, we show that E2 activates ERK through ERa and p38 MAPK stimulation is independent of ERs. We confirmed that E2 is able to abrogate apoptosis through MAPKs in primary cultures of neonate mouse skeletal muscle. Also, we proved that testosterone blocks apoptosis as E2. Typical changes of apoptosis such as nuclear fragmentation, cytoskeleton disorganization, mitochondrial reorganization/dysfunction and cytochrome c release induced by H2O2 were abolished when C2C12 cells were preincubated with testosterone. Further studies are required to establish whether there is a parallelism between the mechanisms triggered by both hormones which might be involved in muscle pathologies associated to apoptosis. The data presented deepen the knowledge on the molecular basis of sex hormone-dependent sarcopenia.