Growth hormone (GH) affects cellular size and signaling pathways related to tumorogenesis processes in the liver of mice exposed to different administration patterns of GH at therapeutic doses

VALQUINTA S; MIQUET JG ; PIAZZA VG; GONZALEZ L ; SOTELO AI ; CICCONI N; TURYN D

Mar del Plata

Congreso; LXI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Sociedad Argentina de Investigación Clínica

Prolonged exposure to growth hormone (GH) in mice is associated with hepatomegaly, due to hypertrophy and hyperplasia of hepatocytes and old GH-transgenic mice frequently develop liver tumors. Alterations in signaling pathways involved in cell growth and proliferation have been related to sustained exposure to GH in young adult transgenic mice. These changes could be a direct effect of prolonged GH action or secondary to the pathologicalcontext produced by hormone excess. Consequently, the aim of this work was to assess if lower levels of GH administered for a limited period would also induce any of these alterations. For that purpose, mice were treated with 6 microg/g of body weight of GH per day between 3 and 8 weeks of age, by two daily injections(intermittent treatment) or by osmotic pumps (continuous treatment). In comparison to controls, intermittent GH-treatment increased body size and induced a proportional enlargement of the liver. Continuous treatment provoked similar effects in males, despite differences did not reach statistical significance. Liver sections were analyzed in search of preneoplastic morphological alterations. Mice intermittently treated with GH exhibiteda significantly lower number of hepatocytes per microscope field, denoting cell enlargement. Continuous treatment produced similar changes, only in males. Activation and protein content of STAT3, which is known to be involved in liver tumorogenesis, was evaluated by immunoblotting. In females, both kinds of GHtreatment slightly increased basal phosphorylation of STAT3, while in males only continuous treatment produced a similar change. A small increment in STAT3 abundance was observed in males exposed to both administration patterns. Therefore, limited exposure to low levels of GH can be associated withhypertrophy of hepatocytes, although hepatomegaly is not evidenced, and sexually dimorphic alterations in the activation of STAT3 that depend on hormone administration pattern are also observed.