Liver oncogenic potential of prolonged growth hormone (GH)-administration to growing mice

CICCONI, NADIA SOFÍA; PIAZZA, VERÓNICA G.; BOJORGE, MARIANA; GONZÁLEZ, LORENA; MIQUET, JOHANNA GABRIELA; ANA ISABEL SOTELO

Mar del Plata

Congreso; Reunión Conjunta SAIC, SAI, SAFIS 2018; 2018

Sociedad Argentina de Investigación Clínica

Growth hormone (GH) participates in multiple biological processes, includinggrowth and metabolism; it is thus administered to children with growth deficiencyand to adults under catabolic states, even if they are not GH-deficient. Due to itsmitogenic and antiapoptotic activities, there is growing concern on its protumorigenicpotential as an adverse effect of its administration in the long term. Toevaluate GH treatment on liver tumor formation, male mice were treated with GHduring the growth period. Since GH is not a potent mitogen per se, a hepatic tumorinductor, diethylnitrosamine (DEN), was also administered before weaning.Livers were removed at 48 weeks of age and were inspected for nodular lesionsthat differ from the surrounding liver parenchyma regarding size, color and texture.Only groups receiving DEN developed macroscopic tumors; GH-treatment alonedid not induce tumor-formation, but given with DEN, increased the number ofhepatic lesions. Liver sections were analyzed in search of preneoplasticmorphological alterations. DEN-treated groups exhibited microscopically dysplasticfoci whereas GH-treatment alone did not generate such alterations. The number ofhepatocytes per microscopic field was increased in the dysplastic foci compared tothe surrounding tissue, denoting smaller cell size inside the foci. Mice treated withGH exhibited larger cell size inside the dysplastic foci, compared to the non-GHtreatedDEN-group. To evaluate hepatocellular proliferation, the expression of proliferating cell nuclear antigen (PCNA) was determined by immunohistochemistry. GH-treated groups exhibited a small although nonsignificant increase of PCNA positive nuclei. Increased cell proliferation was also observed inside dysplastic foci, although differences were significant only in animals that did not receive GH treatment.Consequently, GH-treatment to growing mice per se does not promote tumor formation when the hormone is administered during the growth period at a therapeutic dose. However, GH-treatment could facilitate a pro-tumorigenic environment that would promote carcinogenesis.