Aim: 

17b-estradiol (E2) effects on the reproductive system, bone, and cardiovascular system are quite established, whereas less is known about how modulates the physiology of other tissues. Among other skeletal muscle is expected to be an E2 responsive tissue since it express both isoforms of estrogen receptors (ERa and ERb). Significant gender-related differences are found in myoblast growth and E2 seems to attenuate skeletal muscle damage. At present the E2 ability to modulate myogenic differentiation via specific signalling pathways and the contribution of each ER in governing skeletal muscle differentiation remain unknown.

Methods: 

Rat L6 myoblasts were treated with E2 and the appearance of myogenesis differentiation markers (i.e., myogenin, myosin heavy chain (MHC), and GLUT 4 translocation) and the activation of specific signalling kinases was monitored by Western blot. The specific contribution of each ER isoforms has been evaluated by using ER selective agonists or siRNA specific for ERa.

Results: 

E2 increases the expression of differentiation markers with less efficiency to that reported for Insulin-Like Growth Factor (IGF). This E2-induced effect requires rapid extra-nuclear signals and the presence of ERs, whereas no contribute of IGF receptor has been reported. The E2-induced activation of p38/MAPK, PI3K/Akt, and ERK/MAPK is selectively required for the modulation of differentiation marker levels.

Conclusions: 

All together these data indicate that E2, like other extracellular growth factors, modulates specific signals into the cell affecting the muscle development and physiology. Each ER isoforms give a different contribution to E2-induced differentiation. These data provide the basis of gender-related differences in skeletal muscle recovery after damage and allow to define new molecular targets for muscle degenerative disease treatment.