CONICET | Buscador de Institutos y Recursos Humanos

EFFECT OF GROWTH HORMONE ON ARACHIDONIC ACID METABOLISM AND ITS INVOLVEMENT IN LIVER TUMORIGENESIS MICUCCI, GP; PIAZZA, VG; MARTINEZ CS; SOTELO, AI; TURYN, D; GONZALEZ, L; MIQUET, JG Instituto de Química y Fisicoquímica Biológica, Facultad de Farmacia y Bioquímica, UBA, Argentina. Transgenic mice overexpressing growth hormone (GH) exhibit high incidence of liver tumors and display upregulation of the signaling pathways Erk1/2 and PI3K/Akt, which mediate cell proliferation and survival. These signaling pathways also participate in the activation and expression of enzymes involved in the metabolism of arachidonic acid, including cyclooxygenases (COX) and phospholipase cPLA2a, which are believed to play a role in hepatic carcinogenesis. The objective of this study was to determine the impact that prolonged exposure to GH exerts on COX1 and cPLA2a in the liver. The expression of these enzymes was assessed in the liver of GH-transgenic mice by immunoblotting and qRT-PCR. Young adult mice, which exhibit preneoplastic pathology, and animals of advanced ages, which develop liver tumors, were used. Normal littermates served as controls. Transgenic mice displayed elevated protein levels of COX1, but its gene expression was not altered. Both the protein and mRNA abundance of cPLA2a were higher in transgenic than in normal mice. The results were similar for young and old mice, and were confirmed in both genders. These experiments suggest that prolonged exposure to GH impairs the expression of key enzymes involved in arachidonic acid metabolism, and could contribute to establish the mechanisms involved in the process of liver carcinogenesis in mice overexpressing GH.