{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T11:31:59Z","timestamp":1789471919053,"version":"build-2803163510"},"reference-count":33,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Thyrotropin receptor (TSHR) and insulin-like growth factor 1 receptor (IGF-1R) have been shown to crosstalk in primary cultures of human thyrocytes (hThyros) and Graves\u2019 orbital fibroblasts. The phenomenon of TSHR\/IGF-1R crosstalk has been largely studied in the pathogenesis of thyroid eye disease (TED) in human orbital fibroblasts. Here, we investigated the effects of inhibiting the IGF-1R-mediated contribution to crosstalk by linsitinib (Lins), a small-molecule IGF-1R kinase inhibitor, on TSH-induced regulation of thyroperoxidase (TPO) and thyroglobulin (TG) mRNAs and proteins in hThyros\n                      <jats:italic toggle=\"yes\">in vitro,<\/jats:italic>\n                      and on TPO and TG mRNAs and free thyroxine (fT4) levels\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Steady-state levels of mRNAs of TPO and TG in hThyros\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and mouse thyroid glands were measured by RT-qPCR. Human TG (hTG) and human TPO (hTPO) proteins in human thyroid cell cultures were measured by Western blot or ELISA. Translation rates of hTG were quantified by stable isotope labeling by amino acids method (SILAC). Thyroidal mouse\n                      <jats:italic toggle=\"yes\">Tpo<\/jats:italic>\n                      (m\n                      <jats:italic toggle=\"yes\">Tpo<\/jats:italic>\n                      ) and\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      (m\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      ) mRNAs and fT4 in mice were assessed after Lins administration on 3 consecutive days followed by an intraperitoneal dose of bovine TSH (bTSH) 3 hours prior to drawing blood.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      In primary cultures of hThyros, Lins inhibited bTSH-induced upregulation of hTPO mRNA by 61.5%, and hTPO protein was inhibited by 42.4%. There was no effect of Lins on hTG mRNA, but Lins inhibited the upregulation of secreted and cell-associated hTG protein by 50.1% and 42.2%, respectively, by inhibiting hTG mRNA translation. m\n                      <jats:italic toggle=\"yes\">Tpo<\/jats:italic>\n                      mRNA measured in thyroid glands after treatment with Lins was reduced by 31.5%. There was no effect of Lins on m\n                      <jats:italic toggle=\"yes\">Tg<\/jats:italic>\n                      mRNA, however, Lins decreased fT4 levels in mice under basal (endogenous mTSH levels) and bTSH-treated conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The IGF-1R antagonist Lins inhibited bTSH-stimulated hTG and hTPO protein expression in primary cultures of hThyros and fT4 levels in mice. We suggest that thyroid function studies be monitored when Lins is administered to humans, for example, if it is used to treat TED.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2024.0393","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T12:27:18Z","timestamp":1735043238000},"page":"216-224","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Linsitinib Decreases Thyrotropin-Induced Thyroid Hormone Synthesis by Inhibiting Crosstalk Between Thyroid-Stimulating Hormone and Insulin-Like Growth Factor 1 Receptors in Human Thyrocytes\n                    <i>In Vitro<\/i>\n                    and\n                    <i>In Vivo<\/i>\n                    in Mice"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0933-2637","authenticated-orcid":false,"given":"Alisa","family":"Boutin","sequence":"first","affiliation":[{"name":"Laboratory of Endocrinology and Receptor Biology, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Eliseeva","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Receptor Biology, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Templin","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Receptor Biology, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernice","family":"Marcus-Samuels","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Receptor Biology, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. Eric","family":"Anderson","sequence":"additional","affiliation":[{"name":"Advanced Mass Spectrometry Core, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marvin C.","family":"Gershengorn","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Receptor Biology, Bethesda, Maryland, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5137-1931","authenticated-orcid":false,"given":"Susanne","family":"Neumann","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Receptor Biology, Bethesda, Maryland, 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