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Journal of Pediatric Endocrinology and Metabolism

Editor-in-Chief: Kiess, Wieland

Ed. by Bereket, Abdullah / Darendeliler, Feyza / Dattani, Mehul / Gustafsson, Jan / Luo, Fei Hong / Mericq, Veronica / Ogata, Tsutomu / Toppari, Jorma


IMPACT FACTOR 2017: 1.086

CiteScore 2017: 1.07

SCImago Journal Rank (SJR) 2017: 0.465
Source Normalized Impact per Paper (SNIP) 2017: 0.580

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2191-0251
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Volume 30, Issue 2

Issues

Epidermal growth factor receptor (EGFR) involvement in successful growth hormone (GH) signaling in GH transduction defect

Eirini Kostopoulou
  • Corresponding author
  • Pediatric Endocrine Research Laboratory, Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Patras School of Medicine, Patras, Greece
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  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Andrea Paola Rojas-Gil
  • Faculty of Human Movement and Quality of Life Sciences, Department of Nursing, University of Peloponnese, Sparta, Lakonias, Greece
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/ Alexia Karvela
  • Pediatric Endocrine Research Laboratory, Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Patras School of Medicine, Patras, Greece
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/ Bessie E. Spiliotis
  • Corresponding author
  • Pediatric Endocrine Research Laboratory, Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Patras School of Medicine, Patras, Greece
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  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-01-18 | DOI: https://doi.org/10.1515/jpem-2016-0189

Abstract

Background:

Growth hormone (GH) transduction defect (GHTD) is a growth disorder with impaired signal transducer and activator of transcription 3 (STAT3) phosphorylation mediated by overexpression of cytokine-inducible SH2-containing protein (CIS), which causes increased growth hormone receptor (GHR) degradation. This study investigated the role of epidermal growth factor (EGF) in the restoration of normal GH signaling in GHTD.

Methods:

Protein expression, cellular localization and physical contact of proteins of the GH and EGF signaling pathways were studied by Western immunoblotting, immunofluorescence and co-immunoprecipitation, respectively. These were performed in fibroblasts of one GHTD patient (P) and one control child (C) at the basal state and after induction with human GH (hGH) 200 μg/L (GH200), either with or without silencing of CIS mRNA, and after induction with hGH 1000 μg/L (GH1000) or 50 ng/mL EGF.

Results:

The membrane availability of the EGF receptor (EGFR) and the activated EGFR (pEGFR) was increased in P only after simultaneous GH200 and silencing of CIS mRNA or with GH1000, whereas this occurred in C after GH200 alone. After EGF induction, the membrane localization of GHR, STAT3 and that of EGFR were increased in P more than in C.

Conclusions:

In conclusion, in GHTD, the EGFR seems to participate in successful GH signaling, but induction of GHTD fibroblasts with a higher dose of hGH is needed. The EGF/EGFR pathway, in contrast to the GH/GHR pathway, seems to function normally in P and is more primed compared to C. The involvement of the EGFR in successful GH signaling may explain the catch-up growth seen in the Ps when exogenous hGH is administered.

Keywords: cytokine-inducible SH2-containing protein (CIS); epidermal growth factor receptor (EGFR); GH pathway; growth hormone; growth hormone transduction defect (GHTD); phosphorylated STAT3 (pSTAT3)

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About the article

Corresponding authors: Eirini Kostopoulou, MD, PhD, and Bessie E. Spiliotis, MD, Pediatric Endocrine Research Laboratory, Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, University of Patras School of Medicine, 26504, Rio, Patras, Greece, Phone: +30 6972070117 (E. Kostopoulou); +30 6977000947 (B.E. Spiliotis)


Received: 2016-05-15

Accepted: 2016-11-28

Published Online: 2017-01-18

Published in Print: 2017-02-01


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Journal of Pediatric Endocrinology and Metabolism, Volume 30, Issue 2, Pages 221–230, ISSN (Online) 2191-0251, ISSN (Print) 0334-018X, DOI: https://doi.org/10.1515/jpem-2016-0189.

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