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TSH/IGF-1 Receptor Cross-Talk Rapidly Activates Extracellular Signal-Regulated Kinases in Multiple Cell Types

We previously showed that thyrotropin (TSH)/insulinlike growth factor (IGF)-1 receptor cross-talk appears to be involved in Graves’ orbitopathy (GO) pathogenesis and upregulation of thyroid-specific genes in human thyrocytes. In orbital fibroblasts from GO patients, coadministration of TSH and IGF-1...

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Autores principales: Krieger, Christine C., Perry, Joseph D., Morgan, Sarah J., Kahaly, George J., Gershengorn, Marvin C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659693/
https://www.ncbi.nlm.nih.gov/pubmed/28938449
http://dx.doi.org/10.1210/en.2017-00528
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author Krieger, Christine C.
Perry, Joseph D.
Morgan, Sarah J.
Kahaly, George J.
Gershengorn, Marvin C.
author_facet Krieger, Christine C.
Perry, Joseph D.
Morgan, Sarah J.
Kahaly, George J.
Gershengorn, Marvin C.
author_sort Krieger, Christine C.
collection PubMed
description We previously showed that thyrotropin (TSH)/insulinlike growth factor (IGF)-1 receptor cross-talk appears to be involved in Graves’ orbitopathy (GO) pathogenesis and upregulation of thyroid-specific genes in human thyrocytes. In orbital fibroblasts from GO patients, coadministration of TSH and IGF-1 induces synergistic increases in hyaluronan secretion. In human thyrocytes, TSH plus IGF-1 synergistically increased expression of the sodium-iodide symporter that appeared to involve ERK1/2 activation. However, the details of ERK1/2 activation were not known, nor was whether ERK1/2 was involved in this synergism in other cell types. Using primary cultures of GO fibroblasts (GOFs) and human thyrocytes, as well as human embryonic kidney (HEK) 293 cells overexpressing TSH receptors (HEK-TSHRs), we show that simultaneous activation of TSHRs and IGF-1 receptors (IGF-1Rs) causes rapid, synergistic phosphorylation/activation of ERK1 and ERK2 in all three cell types. This effect is partially inhibited by pertussis toxin, an inhibitor of TSHR coupling to G(i)/G(o) proteins. In support of a role for G(i)/G(o) proteins in ERK1/2 phosphorylation, we found that knockdown of G(i(1–3)) and G(o) in HEK-TSHRs inhibited ERK1/2 phosphorylation stimulated by TSH and TSH plus IGF-1. These data demonstrate that the synergistic effects of TSH plus IGF-1 occur early in the TSHR signaling cascade and further support the idea that TSHR/IGF-1R cross-talk is an important mechanism for regulation of human GOFs and thyrocytes.
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spelling pubmed-56596932018-10-01 TSH/IGF-1 Receptor Cross-Talk Rapidly Activates Extracellular Signal-Regulated Kinases in Multiple Cell Types Krieger, Christine C. Perry, Joseph D. Morgan, Sarah J. Kahaly, George J. Gershengorn, Marvin C. Endocrinology Research Articles We previously showed that thyrotropin (TSH)/insulinlike growth factor (IGF)-1 receptor cross-talk appears to be involved in Graves’ orbitopathy (GO) pathogenesis and upregulation of thyroid-specific genes in human thyrocytes. In orbital fibroblasts from GO patients, coadministration of TSH and IGF-1 induces synergistic increases in hyaluronan secretion. In human thyrocytes, TSH plus IGF-1 synergistically increased expression of the sodium-iodide symporter that appeared to involve ERK1/2 activation. However, the details of ERK1/2 activation were not known, nor was whether ERK1/2 was involved in this synergism in other cell types. Using primary cultures of GO fibroblasts (GOFs) and human thyrocytes, as well as human embryonic kidney (HEK) 293 cells overexpressing TSH receptors (HEK-TSHRs), we show that simultaneous activation of TSHRs and IGF-1 receptors (IGF-1Rs) causes rapid, synergistic phosphorylation/activation of ERK1 and ERK2 in all three cell types. This effect is partially inhibited by pertussis toxin, an inhibitor of TSHR coupling to G(i)/G(o) proteins. In support of a role for G(i)/G(o) proteins in ERK1/2 phosphorylation, we found that knockdown of G(i(1–3)) and G(o) in HEK-TSHRs inhibited ERK1/2 phosphorylation stimulated by TSH and TSH plus IGF-1. These data demonstrate that the synergistic effects of TSH plus IGF-1 occur early in the TSHR signaling cascade and further support the idea that TSHR/IGF-1R cross-talk is an important mechanism for regulation of human GOFs and thyrocytes. Endocrine Society 2017-08-11 /pmc/articles/PMC5659693/ /pubmed/28938449 http://dx.doi.org/10.1210/en.2017-00528 Text en
spellingShingle Research Articles
Krieger, Christine C.
Perry, Joseph D.
Morgan, Sarah J.
Kahaly, George J.
Gershengorn, Marvin C.
TSH/IGF-1 Receptor Cross-Talk Rapidly Activates Extracellular Signal-Regulated Kinases in Multiple Cell Types
title TSH/IGF-1 Receptor Cross-Talk Rapidly Activates Extracellular Signal-Regulated Kinases in Multiple Cell Types
title_full TSH/IGF-1 Receptor Cross-Talk Rapidly Activates Extracellular Signal-Regulated Kinases in Multiple Cell Types
title_fullStr TSH/IGF-1 Receptor Cross-Talk Rapidly Activates Extracellular Signal-Regulated Kinases in Multiple Cell Types
title_full_unstemmed TSH/IGF-1 Receptor Cross-Talk Rapidly Activates Extracellular Signal-Regulated Kinases in Multiple Cell Types
title_short TSH/IGF-1 Receptor Cross-Talk Rapidly Activates Extracellular Signal-Regulated Kinases in Multiple Cell Types
title_sort tsh/igf-1 receptor cross-talk rapidly activates extracellular signal-regulated kinases in multiple cell types
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5659693/
https://www.ncbi.nlm.nih.gov/pubmed/28938449
http://dx.doi.org/10.1210/en.2017-00528
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