Effects of long-term intermittent administration of GH on EGF signaling in liver

DÍAZ ME; MIQUET JG; SOTELO AI; TURYN D; GONZÁLEZ L

Harrogate

Congreso; Annual Meeting of the British Endocrine Society (BES 2012); 2012

Society for Endocrinology

Growth hormone (GH) is involved in body growth and metabolism. This hormone is used for the treatment of various clinical conditions and is administrated subcutaneously once daily or 3 times a week. The chronic use of GH has side effects; among them, the increase in tumor incidence. GH activates pathways related with oncogenesis not only by the activation of its specific receptor, but also by transactivation and regulation of the expression of the epidermal growth factor receptor (EGFR). The aim of this work was to analyze the effects of long-term intermittent administration of GH on the EGF signaling in liver. In order to achieve this goal, female Swiss mice were injected subcutaneously with GH (1 mg/kg body weight) twice a day during one week. After treatment, the animals received an acute stimulus of EGF or saline 10 minutes before sacrifice to evaluate the effects of prolonged exposure to GH over EGF signaling pathways. An increase of the EGFR protein content in GH treated mice was found. EGFR phosphorylation on tyrosine residues after the EGF stimulus was increased in mice treated with GH. These animals also showed a slight increase in the activation of Erk1/2 and Akt, and a very significant increase in the activation of STAT3 and STAT5 by EGF, while the content of these proteins did not change after treatment with GH. The intermittent administration of GH stimulates the expression of the major urinary proteins (MUPs), which evidenced the pulsatile pattern of injected GH. In conclusion, intermittent administration of GH increases expression of EGFR and activation of its signaling pathways, specially the STATs.