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

PIAZZA VG, MARTINEZ CS, GONZ¨¢LEZ L, TURYN D, MIQUET JG, SOTELO AI.

Bariloche

Simposio; The Second South American Spring Symposium in Signal Transduction and Molecular Medicine (SISTAM);; 2012

South American Spring Symposium in Signal Transduction and Molecular Medicine (SISTAM);

Role of PI3K/Akt and MAPK signaling pathways during the growth period in muscle of mice overexpressing growth hormone. Piazza VG, Martinez CS, Gonz¨¢lez L, Turyn D, Miquet JG, Sotelo AI Instituto de Qu¨ªmica y Fisicoqu¨ªmica Biol¨®gicas (IQUIFIB), UBA-CONICET, Facultad de Farmacia y Bioqu¨ªmica. Jun¨ªn 956, C1113AAD, Buenos Aires, Argentina. veronicagpiazza@gmail.com   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, PI3K/Akt/GSK3¦Â and MEK/ERK1/2, both involved in protein synthesis, cell survival and proliferation. Transgenic mice overexpressing GH have higher circulating GH levels than normal mice since birth, but no significant differences in body size are observed until the third week of age. The aim of this work was to study the activation of PI3K/Akt/GSK3¦Â and MEK/ERK1/2 during the growth period in muscle of GH-transgenic mice to investigate potential molecular mechanisms involved in the age-dependent growth response to this hormone. In order to evaluate mediators of these signaling pathways, muscle was extracted from GH-transgenic mice and its normal siblings of 2 weeks (GH-independent growth), 4 weeks (GH-dependent growth) and 9 weeks old (young adult, control) and protein activation/content was assayed by immunoblotting. We observed higher protein levels of Akt and ERK1/2 in pups compared to young adults. No difference was observed in GSK3¦Â levels. Activation of Akt and ERK1/2 decreased with age; there was no significant difference between genotypes. GSK3¦Â showed a different profile: its phosphorylation was higher in 4 weeks transgenic mice respect to 2 and 9 weeks old mice, whereas no difference was observed between normal mice. In conclusion, the highest activation of these signaling pathways is achieved during the GH-independent period of body growth, in spite transgenic mice exhibit elevated levels of circulating GH throughout life.