Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2008) 15 P107

SFEBES2008 Poster Presentations Cytokines and growth factors (7 abstracts)

Transgenic mice overexpressing growth hormone (GH) exhibit hepatic upregulation of GH-signalling mediators involved in cell proliferation, migration and survival

Johanna G Miquet 1 , Lorena González 1 , Elsa Zotta 2 , Andrzej Bartke 3 , Daniel Turyn 1 & Ana I Sotelo 1

1Department of Biological Chemistry, School of Pharmacy and Biochemistry and 2Department of Physiology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina; 3Department of Internal Medicine and Physiology, School of Medicine, Southern Illinois University, Springfield, Illinois, USA.

Chronically elevated GH levels in GH-transgenic mice derive in accelerated growth and increased body weight. These animals present increased circulating IGF-I and hepatic IGF-I mRNA levels, as well as liver enlargement due to hypertrophy and hyperplasia, which frequently progress to hepatomas as the animals age.

We have previously described that the GH-induced JAK2/STAT5 signalling pathway is desensitized in the liver of transgenic mice overexpressing GH. Therefore, in the present study we have evaluated other GH signalling pathways that could be activated in GH-transgenic mice liver. Animals received GH (5 mg/kg) or saline i.p. injection, 7.5 min later they were euthanized and the liver removed. Normal siblings were used as controls. The signalling mediators of interest were analyzed by immunoprecipitation and western-blotting; for c-Src, an in vitro kinase assay was also performed.

GH administration induced an important increment in STAT3 phosphorylation level in normal mice, but transgenic mice did not respond to GH stimulation. However, STAT3 was constitutively phosphorylated in transgenic mice, whereas its protein content was not increased. GH transgenic mice displayed overexpression of the tyrosine kinase c-Src, accompanied by an elevation of its activity. Other signalling mediators including FAK, EGFR, Erk1/2, Akt and mTOR displayed elevated protein and basal phosphorylation levels in transgenic animals. However, none of these mediators were activated upon GH acute stimulation.

Thus, GH-overexpressing transgenic mice exhibit hepatic upregulation of signalling mediators related to cell proliferation, survival and migration. The upregulation of these proteins may represent GH signalling pathways that are constitutively activated in the presence of sustained exposure to elevated GH levels. These molecular alterations could be implicated in the liver pathological alterations and increased susceptibility of hepatomas observed in GH-transgenic mice.

Article tools

My recent searches

No recent searches.