Growth hormone (GH)-signaling through Jak2/Stat5 pathway in muscle of growing GH-transgenic mice.

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

Buenos Aires

Congreso; Congreso anual de la Sociedad Argentina de Investigaciones Bioquímicas (SAIB); 2013

Sociedad Argentina de Investigaciones Bioquímicas (SAIB)

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.