17 -Estradiol regulates the first steps of skeletal muscle cell differentiation via ER- -mediated signals

Galluzzo P, Rastelli C, Bulzomi P, Acconcia F, Pallottini V, Marino M. 17 beta-Estradiol regulates the first steps of skeletal muscle cell differentiation via ER-alpha-mediated signals. Am J Physiol Cell Physiol 297: C1249-C1262, 2009. First published September 2, 2009; doi:10.1152/ajpcell.00188.2009.-17 beta-Estradiol (E-2) mediates a wide variety of complex biological processes determining the growth and development of reproductive tract as well as nonreproductive tissues of male and female individuals. While E-2 effects on the reproductive system, bone, and cardiovascular system are quite well established, less is known about how it affects the physiology of other tissues. Skeletal muscle is a tissue that is expected to be E-2 responsive since both isoforms of estrogen receptor (ER-alpha and ER-beta) are expressed. Significant sex-related differences have been described in skeletal muscle, although the role played by E-2 and the mechanisms underlying it remain to be determined. Here, we demonstrate that E-2 increases the glucose transporter type 4 translocation at membranes as well as the expression of well-known differentiation markers of myogenesis (i.e., myogenin and myosin heavy chain) in rat myoblast cells (L6). These E-2-induced effects require rapid extranuclear signals and the presence of ER-alpha, whereas no contribution of IGF-I receptor has been observed. In particular, ER-alpha-dependent Akt activation participates in regulating the first step of myogenic differentiation. Moreover, both receptors mediate the E-2-induced activation of p38, which, in turn, affects the expression of myogenin and myosin heavy chain. All together, these data indicate that E-2 should be included in the list of skeletal muscle trophic factors.