Señalización de la hormona de crecimiento (GH) en hígado de ratones expuestos a concentraciones suprafisiológicas de GH : relación con el desarrollo de tumores hepáticos
Growth Hormone (GH) promotes postnatal body growth. At the cellular\nlevel, it activates signaling pathways related to growth, proliferation and survival\nprocesses. Particularly, transgenic mice overexpressing GH exhibit dysregulation\nof GH-signaling since early ages and higher incidence of hepato...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Facultad de Farmacia y Bioquímica
2018
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_2099 http://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_2099.dir/2099.PDF |
| Aporte de: |
| Sumario: | Growth Hormone (GH) promotes postnatal body growth. At the cellular\nlevel, it activates signaling pathways related to growth, proliferation and survival\nprocesses. Particularly, transgenic mice overexpressing GH exhibit dysregulation\nof GH-signaling since early ages and higher incidence of hepatocellular\ncarcinoma during late adulthood. Pharmacological doses of GH are currently\nadministered to children with retarded growth, related or not to GH deficiency.\nGiven that there are no conclusive studies regarding the relationship of these\ntreatments with the development of tumors, we analyzed the molecular\nmechanisms triggered by a pharmacological dose of GH, intermittently or\ncontinuously administered, which could be related to this process. In normal\ngrowing mice, a low and intermittent dose of GH, sufficient to promote body\ngrowth, did not induce relevant changes in the activation of GH-signaling\npathways in the liver. However, in females, it increased the epidermal growth\nfactor receptor content and its response capability. The same dose\nadministered in a sustained way generated molecular alterations similar to\nthose observed in growing GH-transgenic mice, even when it did not promote\nbody growth. These results showed that GH-treatment could provide a protumorigenic\nenvironment by mechanisms tightly related to circulating GH\nconcentration pattern. |
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