17beta-Estradiol regulates the first steps of skeletal muscle cell differentiation via ER-alpha-mediated signals.
17beta-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.
Galluzzo
Paola
P
Department of Biology, University Roma Tre, I-00146 Rome, Italy.
Rastelli
Chiara
C
Bulzomi
Pamela
P
Acconcia
Filippo
F
Pallottini
Valentina
V
Marino
Maria
M
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D004958:Estradiol / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology* / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism; D018008:Myogenin / Q000096:biosynthesis; D018995:Myosin Heavy Chains / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D051275:Glucose Transporter Type 4; D018008:Myogenin; D004958:Estradiol; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; D018995:Myosin Heavy Chains