Role of PI3K/Akt and MAPK signaling pathways during the growth period in muscle of mice overexpressing growth hormone.

PIAZZA VG; MARTINEZ CS; GONZÁLEZ L; TURYN D; MIQUET JG; SOTELO AI

San Carlos de Bariloche

Simposio; The Second South American Spring Symposium in Signal Transduction and Molecular Medicine.; 2012

Growth hormone (GH) transgenic mice (Tg) present higher GH serum levels than normal siblings (N) since birth but no phenotypic differences are observed until the third week of age when GH- dependent growth begins. JAK2/STAT5 is the main GH signaling pathway related to body growth; muscle and bone are the principal tissues implicated in this process. In order to asses potential molecular mechanisms involved in the age-dependent growth response to GH, 2 weeks (before GH- dependent growth), 4 weeks (GH-dependent growth) and 9 weeks old (young adult, control) Tg and N mice received an acute stimulus of GH and were sacrificed after 30 minutes. Muscle was extracted and protein activation/content was assayed by immunoblotting. Whereas N mice show high STAT5 phosphorylation levels in response to GH stimulus, with the highest response during the growth period, Tg mice do not respond at any age studied, accompanied by low levels of GHR and high levels of negative modulators. Maximal endogenous STAT5 phosphorylation was found in 2 weeks old mice, with a slight increase in Tg mice at every age studied. Pups also present high levels of negative modulators which could be restraining GH action at this age. As the activation of JAK2/STAT5 signaling pathway is restricted in Tg mice muscle, other GH-activated pathways would be responsible for the exacerbated growth seen in these mice.