Autocrine growth hormone production prevents apoptosis and inhibits differentiation in C2C12 myoblasts.
Although C2C12 myoblasts express low levels of growth hormone receptor (GHR), we failed to see any effect of exogenous growth hormone (GH) on cell proliferation or differentiation. C2C12 cells stably overexpressing (sixfold) more in GHR (C2C12(GHR)) grew faster than parental cells in media containing 2% serum, and proliferated while parental cells died, in the absence of serum. These effects were independent of exogenous GH but were inhibited by anti-GH and anti-insulin-like growth factor (anti-IGF-1) antibodies, consistent with a local production of GH, which we confirmed by RT-PCR and radioimmunoassay. In C2C12(GHR) cells, we observed an increased activation of the Janus kinase 2 (Jak2), signal transducers and activator of transcription 5 (Stat5), mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) upon acute GH stimulation. GHR overexpression also inhibited the formation of myotubes and the expression of markers for myoblast differentiation. Taken together, our data suggest that GH acts as an autocrine factor in C2C12 cells, to enhance proliferation and to inhibit differentiation.
Segard
Haniaa Bouzinba
HB
INSERM Unit 344, Molecular Endocrinology, Faculty of Medicine Necker, Paris, France.
Moulin
Stéphanie
S
Boumard
Stéphanie
S
Augier de Crémiers
Catherine
C
Kelly
Paul A
PA
Finidori
Joëlle
J
D000818:Animals; D017209:Apoptosis; D019898:Autocrine Communication; D002454:Cell Differentiation; D002460:Cell Line; D016895:Culture Media, Serum-Free; D004247:DNA / Q000096:biosynthesis; D013006:Growth Hormone / Q000096:biosynthesis / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010641:Phenotype; D011986:Receptors, Somatotropin / Q000235:genetics; D014162:Transfection
D016895:Culture Media, Serum-Free; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D004247:DNA