ArticleThyroid : official journal of the American Thyroid Association2016
Thyrotropin and Insulin-Like Growth Factor 1 Receptor Crosstalk Upregulates Sodium-Iodide Symporter Expression in Primary Cultures of Human Thyrocytes.
Article in Thyroid : official journal of the American Thyroid Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Change in insulin-like growth factor type 1 concentration after radioactive iodine treatment in cats with hyperthyroidism.Journal of feline medicine and surgery · 2025Article
- TSH upregulates CYP4B1 through the PI3K/AKT/CREB pathway to promote cardiac hypertrophy.Journal of endocrinological investigation · 2025Article
- Linsitinib Decreases Thyrotropin-Induced Thyroid Hormone Synthesis by Inhibiting Crosstalk Between Thyroid-Stimulating Hormone and Insulin-Like Growth Factor 1 Receptors in Human ThyrocytesThyroid : official journal of the American Thyroid Association · 2025Article
- Pathogenesis and Management Strategies in Radioiodine-Refractory Differentiated Thyroid Cancer: From Molecular Mechanisms Toward Therapeutic Approaches: A Comprehensive Review.Journal of clinical medicine · 2024Review
- Advances of IGF-1R inhibitors in Graves' ophthalmopathy.International ophthalmology · 2024Review
- Defining theThyroid : official journal of the American Thyroid Association · 2024Article
- GLIS3 expression in the thyroid gland in relation to TSH signaling and regulation of gene expression.Cellular and molecular life sciences : CMLS · 2024Article
- Primary human thyrocytes maintained the function of thyroid hormone production and secretion in vitro.Journal of endocrinological investigation · 2023Article
- Targeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular docking for drug discovery.BMC endocrine disorders · 2023Article
- Efficacy and Safety of 6-Weekly versus 12-Weekly Intravenous Methylprednisolone in Moderate-to-Severe Active Thyroid-Associated Ophthalmopathy.Journal of clinical medicine · 2023Article
- Linsitinib, an IGF-1R inhibitor, attenuates disease development and progression in a model of thyroid eye disease.Frontiers in endocrinology · 2023Article
- Opposing Effects of EGF Receptor Signaling on Proliferation and Differentiation Initiated by EGF or TSH/EGF Receptor Transactivation.Endocrinology · 2022Article
- TSH stimulation of human thyroglobulin and thyroid peroxidase gene transcription is partially dependent on internalization.Cellular signalling · 2022Article
- Review
- Proximity ligation assay to study TSH receptor homodimerization and crosstalk with IGF-1 receptors in human thyroid cells.Frontiers in endocrinology · 2022Article
- Graves' Autoantibodies Exhibit Different Stimulating Activities in Cultures of Thyrocytes and Orbital Fibroblasts Not Reflected by Clinical Assays.Thyroid : official journal of the American Thyroid Association · 2022Article
- Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion.Frontiers in endocrinology · 2022Review
- Adiponectin and Thyroid Cancer: Insight into the Association between Adiponectin and Obesity.Aging and disease · 2021Review
- Thyrotropin regulation of differentiated gene transcription in adult human thyrocytes in primary culture.Molecular and cellular endocrinology · 2020Article
- Targeting TSH and IGF-1 Receptors to Treat Thyroid Eye Disease.European thyroid journal · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMajor regulation of thyroid gland function is mediated by thyrotropin (TSH) activating the TSH receptor (TSHR) and inducing upregulation of genes involved in thyroid hormone synthesis. Evidence suggests that the insulin-like growth factor 1 (IGF-1) receptor (IGF-1R) may play a role in regulating TSHR functional effects. This study examined the potential role of TSHR/IGF-1R crosstalk in primary cultures of human thyrocytes.
resultsTSH/IGF-1 co-treatment elicited additive effects on thyroglobulin (TG), thyroperoxidase (TPO), and deiodinase type 2 (DIO2) mRNA levels but synergistic effects on sodium-iodide symporter (NIS) mRNA. Similar cooperativity was seen on the level of TG protein secretion (additive) and NIS protein expression (synergistic). The IGF-1R tyrosine kinase inhibitor linsitinib inhibited TSH-stimulated upregulation of NIS but not TG, indicating that NIS regulation is in part IGF-1R dependent and occurs via receptor crosstalk. Cooperativity was not seen at the level of cAMP/protein kinase A (PKA) signaling, IGF-1R phosphorylation, or Akt activation. However, TSH and IGF-1 synergistically activated ERK1/2. Pharmacological inhibition of ERK1/2 by the MEK1/2 inhibitor U0126 and of Akt by MK-2206 virtually abolished NIS stimulation by TSH and the synergistic effect of IGF-1.
conclusionAs linsitinib inhibited upregulation of NIS stimulated by TSH alone, it is concluded that crosstalk between TSHR and IGF-1R, without agonist activation of IGF-1R, plays a role in NIS regulation in human thyrocytes via a mechanism involving ERK1/2 and/or Akt. Fully understanding the nature of this crosstalk has clinical implications for the treatment of thyroid diseases, including thyroid cancer.
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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.