Epidermal growth factor receptor (EGFR) involvement in successful growth hormone (GH) signaling in GH transduction defect
-
Eirini Kostopoulou
,
Andrea Paola Rojas-Gil
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.
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.
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©2017 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review
- Definition of insulin resistance affects prevalence rate in pediatric patients: a systematic review and call for consensus
- Mini Review
- Bone health assessment of food allergic children on restrictive diets: a practical guide
- Original Articles
- Plasma concentrations of osteocalcin are associated with the timing of pubertal progress in boys
- The role of season and climate in the incidence of congenital hypothyroidism in Kerman province, Southeastern Iran
- Seven cases with Williams-Beuren syndrome: endocrine evaluation and long-term follow-up
- The association between obesity, hypertension and left ventricular mass in adolescents
- Bone mineral density and bone metabolic markers’ status in children with neurofibromatosis type 1
- The prevalence of dyslipidemia and associated factors in children and adolescents with type 1 diabetes
- High predictability of impaired glucose tolerance by combining cardiometabolic screening parameters in obese children
- Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children
- Prevalence, risk factors and consequences of overweight and obesity among schoolchildren: a cross-sectional study in Kashmir, India
- Association between screen time and snack consumption in children and adolescents: The CASPIAN-IV study
- Epidermal growth factor receptor (EGFR) involvement in successful growth hormone (GH) signaling in GH transduction defect
- Case Reports
- Turner syndrome and pituitary adenomas: a case report and review of literature
- An ignored cause of red urine in children: rhabdomyolysis due to carnitine palmitoyltransferase II (CPT-II) deficiency
- Beta cell function and clinical course in three siblings with thiamine-responsive megaloblastic anemia (TRMA) treated with thiamine supplementation
- Glycogen storage disease type IX and growth hormone deficiency presenting as severe ketotic hypoglycemia
Artikel in diesem Heft
- Frontmatter
- Review
- Definition of insulin resistance affects prevalence rate in pediatric patients: a systematic review and call for consensus
- Mini Review
- Bone health assessment of food allergic children on restrictive diets: a practical guide
- Original Articles
- Plasma concentrations of osteocalcin are associated with the timing of pubertal progress in boys
- The role of season and climate in the incidence of congenital hypothyroidism in Kerman province, Southeastern Iran
- Seven cases with Williams-Beuren syndrome: endocrine evaluation and long-term follow-up
- The association between obesity, hypertension and left ventricular mass in adolescents
- Bone mineral density and bone metabolic markers’ status in children with neurofibromatosis type 1
- The prevalence of dyslipidemia and associated factors in children and adolescents with type 1 diabetes
- High predictability of impaired glucose tolerance by combining cardiometabolic screening parameters in obese children
- Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children
- Prevalence, risk factors and consequences of overweight and obesity among schoolchildren: a cross-sectional study in Kashmir, India
- Association between screen time and snack consumption in children and adolescents: The CASPIAN-IV study
- Epidermal growth factor receptor (EGFR) involvement in successful growth hormone (GH) signaling in GH transduction defect
- Case Reports
- Turner syndrome and pituitary adenomas: a case report and review of literature
- An ignored cause of red urine in children: rhabdomyolysis due to carnitine palmitoyltransferase II (CPT-II) deficiency
- Beta cell function and clinical course in three siblings with thiamine-responsive megaloblastic anemia (TRMA) treated with thiamine supplementation
- Glycogen storage disease type IX and growth hormone deficiency presenting as severe ketotic hypoglycemia
