Growth hormone administration patterns differently regulate epidermal growth factor signaling

DÍAZ ME; MIQUET JG; ROSSI SP; IRENE PE; SOTELO AI; FRUNGIERI MB; TURYND; GONZÁLEZ L

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2014 p. 317 - 331

0022-0795

Current growth hormone (GH) administration protocols require frequent subcutaneous injections, resulting in suboptimal compliance. Therefore, there is interest in developing delivery systems for sustained release of the hormone. However, GH has different actions depending on its continuous or pulsatile plasma concentration pattern. GH levels and circulating concentration patterns would be involved in the regulation of epidermal growth factor receptor (EGFR) expression in liver. Aberrant expression of this receptor and/or its hyperactivation have been associated with pathogenesis of different types of carcinoma. Considering that one of the adverse effects associated with GH overexpression and chronic use of GH is the increased incidence of malignancies, the aim of this study was to analyze the effects of GH plasma concentration patterns on EGFR expression and signaling in mice liver. For this purpose, GH was administered by subcutaneous daily injections to produce an intermittent plasma pattern or by osmotic pumps to provoke a continuous GH concentration. Results showed that intermittent injections of GH induced an upregulation of liver EGFR content, augmented the response to EGF and the induction of proteins involved in cell proliferation promotion in female mice. On the contrary, continuous GH delivery in male mice was associated with diminished EGFR liver content and decreased EGF induced signaling and expression of early genes. Results suggest that sustained delivery systems that allow continuous GH plasma patterns would be beneficial in terms of treatment safety referred to its actions on EGFR signaling and its promitogenic activity.