ArticleMolecular endocrinology (Baltimore, Md.)2014
Human GH receptor-IGF-1 receptor interaction: implications for GH signaling.
Article in Molecular endocrinology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Growth Hormone and Brain Regeneration: Evidence from Clinical Studies in Dementia, Traumatic Brain Injury, and Stroke: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Local growth hormone promotes benign prostatic hyperplasia.JCI insight · 2026Article
- Article
- Growth hormone and radiation therapy: friend, foe, or both?Endocrine-related cancer · 2024Review
- Efficacy and Safety of Nasal Immunisation with Somatostatin DNA Vaccine for Growth Promotion in Fattening Pigs.Animals : an open access journal from MDPI · 2022Article
- Mutations inGenes · 2022Review
- IGF Signaling in Intervertebral Disc Health and Disease.Frontiers in cell and developmental biology · 2021Review
- Dual Characters of GH-IGF1 Signaling Pathways in Radiotherapy and Post-radiotherapy Repair of Cancers.Frontiers in cell and developmental biology · 2021Review
- Classical and novel GH receptor signaling pathways.Molecular and cellular endocrinology · 2020Review
- Autocrine/paracrine actions of growth hormone in human melanoma cell lines.Biochemistry and biophysics reports · 2020Article
- Therapeutic Targeting of the IGF Axis.Cells · 2019Review
- Growth hormone (GH) receptor (GHR)-specific inhibition of GH-Induced signaling by soluble IGF-1 receptor (sol IGF-1R).Molecular and cellular endocrinology · 2019Article
- Growth Hormone Induces Colon DNA Damage Independent of IGF-1.Endocrinology · 2019Article
- Excess growth hormone suppresses DNA damage repair in epithelial cells.JCI insight · 2019Article
- Article
- Growth hormone-releasing hormone (GHRH) and its agonists inhibit hepatic and tumoral secretion of IGF-1.Oncotarget · 2018Article
- Construction and analysis of gene-gene dynamics influence networks based on a Boolean model.BMC systems biology · 2017Article
- Height, selected genetic markers and prostate cancer risk: results from the PRACTICAL consortium.British journal of cancer · 2017Article
- Skeletal effects of growth hormone and insulin-like growth factor-I therapy.Molecular and cellular endocrinology · 2016Review
- Growth hormone is permissive for neoplastic colon growth.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
Corrections and comments
- Erratum issuedErratum.2015
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
GH signaling yields multiple anabolic and metabolic effects. GH binds the transmembrane GH receptor (GHR) to activate the intracellular GHR-associated tyrosine kinase, Janus kinase 2 (JAK2), and downstream signals, including signal transducer and activator of transcription 5 (STAT5) activation and IGF-1 gene expression. Some GH effects are partly mediated by GH-induced IGF-1 via IGF-1 receptor (IGF-1R), a tyrosine kinase receptor. We previously demonstrated in non-human cells that GH causes formation of a GHR-JAK2-IGF-1R complex and that presence of IGF-1R (even without IGF-1 binding) augments proximal GH signaling. In this study, we use human LNCaP prostate cancer cells as a model system to further study the IGF-1R's role in GH signaling. GH promoted JAK2 and GHR tyrosine phosphorylation and STAT5 activation in LNCaP cells. By coimmunoprecipitation and a new split luciferase complementation assay, we find that GH augments GHR/IGF-1R complex formation, which is inhibited by a Fab of an antagonistic anti-GHR monoclonal antibody. Short hairpin RNA-mediated IGF-1R silencing in LNCaP cells reduced GH-induced GHR, JAK2, and STAT5 phosphorylation. Similarly, a soluble IGF-1R extracellular domain fragment (sol IGF-1R) interacts with GHR in response to GH and blunts GH signaling. Sol IGF-1R also markedly inhibits GH-induced IGF-1 gene expression in both LNCaP cells and mouse primary osteoblast cells. On the basis of these and other findings, we propose a model in which IGF-1R augments GH signaling by allowing a putative IGF-1R-associated molecule that regulates GH signaling to access the activated GHR/JAK2 complex and envision sol IGF-1R as a dominant-negative inhibitor of this IGF-1R-mediated augmentation. Physiological implications of this new model are discussed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.