title: Growth hormone promotes skeletal muscle cell fusion independent of insulin-like growth factor 1 up-regulation.
abstract: Growth hormone (GH) participates in the postnatal regulation of skeletal muscle growth, although the mechanism of action is unclear. Here we show that the mass of skeletal muscles lacking GH receptors is reduced because of a decrease in myofiber size with normal myofiber number. GH signaling controls the size of the differentiated myotubes in a cell-autonomous manner while having no effect on size, proliferation, and differentiation of the myoblast precursor cells. The GH hypertrophic action leads to an increased myonuclear number, indicating that GH facilitates fusion of myoblasts with nascent myotubes. NFATc2, a transcription factor regulating this phase of fusion, is required for GH action because GH is unable to induce hypertrophy of NFATc2-/- myotubes. Finally, we provide three lines of evidence suggesting that GH facilitates cell fusion independent of insulin-like growth factor 1 (IGF-1) up-regulation. First, GH does not regulate IGF-1 expression in myotubes; second, GH action is not mediated by a secreted factor in conditioned medium; third, GH and IGF-1 hypertrophic effects are additive and rely on different signaling pathways. Taken together, these data unravel a specific function of GH in the control of cell fusion, an essential process for muscle growth.
authors: Institut National de la Santé et de la Recherche Médicale, U810, and Faculté de Médecine Necker-Enfants Malades, Université Paris 5, F-75730 Paris, France. sotiropoulos@necker.fr
authors: Athanassia
authors: A
authors: Sotiropoulos
authors: Mickaël
authors: M
authors: Ohanna
authors: Cécile
authors: C
authors: Kedzia
authors: Ram K
authors: RK
authors: Menon
authors: John J
authors: JJ
authors: Kopchick
authors: Paul A
authors: PA
authors: Kelly
authors: Mario
authors: M
authors: Pende