CONICET | Buscador de Institutos y Recursos Humanos

Growth hormone (GH) is produced by the pituitary gland andit is involved in longitudinal growth promotion and metabolicprocesses. GH exerts many of its physiological functions directlyand indirectly through the synthesis and release of insulin-likegrowth factor I (IGF-I). GH and IGF-I have an essential role inpromoting normal growth and breast development. However, theGH/IGF-I axis has also been widely associated with mammarytumorigenesis. The aim of this work was to study the cellular andmolecular effects of high GH levels in mammary gland that couldbe linked to the mitogenic effects of the hormone. Two animal modelswere used, transgenic mice that overexpress GH and normalmice treated with injections of the hormone in supraphysiologicaldoses during one week. In order to study the molecular effects,the protein content of receptors involved in cell proliferation suchas the GH receptor (GHR), the epidermal growth factor receptor(EGFR), the receptor for insulin like growth factor (IGF-IR) andestrogen receptor alpha (ERalpha) were assed. Additionally, theprotein expression of transcription factors that induce cell proliferationlike c-Myc, c-Fos and c-Jun and the mRNA levels of cyclinD1 were studied. The cellular effects of GH were analyzed byhistological analysis. The results showed a significant decrease inprotein content of GHR in transgenic mice and a marked increasein IGF-IR and EGFR levels in both animal models. No significantdifferences in the protein content of the estrogen receptor wereverified. The levels of c-Fos were increased in transgenic mice andin animals treated with GH during one week, but c-Myc and c-Junwere not modified by high GH levels. Regarding cyclin D1 mRNAamount, transgenic mice showed an increased compared withnormal mice. The histological analysis showed breast epithelialhyperplasia in the transgenic mice but no histological effects ofexogenous GH administration were evidenced.