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

PIAZZA VG; MARTINEZ CS; GONZALEZ 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) promotes longitudinal body growth acting mainly on liver, muscle and bone. It exerts its actions via its membrane receptor which activates JAK2/STAT5, the main GH-signaling pathway related to IGF-1 synthesis and body growth. Suppressors of cytokine signaling (SOCS/CIS) and tyrosine phosphatases (PTP-1B, SHP1/2) contribute to signaling ending. GH-transgenic mice (T) 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. The aim of this work was to evaluate potential molecular mechanisms involved in the age dependent growth response to GH in skeletal muscle and the exacerbated growth seen in transgenic mice. Whereas N mice show high STAT5 phosphorylation levels in response to GH stimulus, with the highest response during the growth period, T 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 T 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 T mice muscle, other GH-activated pathways would be responsible for the exacerbated growth seen in these mice.