{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:17:20Z","timestamp":1792271840041,"version":"4.4.0"},"reference-count":35,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context:<\/jats:title>\n                    <jats:p>The TSH receptor (TSHR) is considered the main target of stimulatory autoantibodies in the pathogenesis of Graves' ophthalmopathy (GO); however, it has been suggested that stimulatory IGF-1 receptor (IGF-1R) autoantibodies also play a role.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>We previously demonstrated that a monoclonal stimulatory TSHR antibody, M22, activates TSHR\/IGF-1R cross talk in orbital fibroblasts\/preadipocytes obtained from patients with GO (GO fibroblasts [GOFs]). We show that cross talk between TSHR and IGF-1R, not direct IGF-1R activation, is involved in the mediation of GO pathogenesis stimulated by Graves' autoantibodies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design\/Setting\/Participants:<\/jats:title>\n                    <jats:p>Immunoglobulins were purified from the sera of 57 GO patients (GO-Igs) and tested for their ability to activate TSHR and\/or IGF-1R directly and TSHR\/IGF-1R cross talk in primary cultures of GOFs. Cells were treated with M22 or GO-Igs with or without IGF-1R inhibitory antibodies or linsitinib, an IGF-1R kinase inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main Outcome Measures:<\/jats:title>\n                    <jats:p>Hyaluronan (hyaluronic acid [HA]) secretion was measured as a major biological response for GOF stimulation. IGF-1R autophosphorylation was used as a measure of direct IGF-1R activation. TSHR activation was determined through cAMP production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>A total of 42 out of 57 GO-Ig samples stimulated HA secretion. None of the GO-Ig samples exhibited evidence for IGF-1R autophosphorylation. Both anti-IGF-1R antibodies completely inhibited IGF-1 stimulation of HA secretion. By contrast, only 1 IGF-1R antibody partially blocked HA secretion stimulated by M22 or GO-Igs in a manner similar to linsitinib, whereas the other IGF-1R antibody had no effect on M22 or GO-Ig stimulation. These findings show that the IGF-1R is involved in GO-Igs stimulation of HA secretion without direct activation of IGF-1R.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>IGF-1R activation by GO-Igs occurs via TSHR\/IGF-1R cross talk rather than direct binding to IGF-1R, and this cross talk is important in the pathogenesis of GO.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/jc.2016-1315","type":"journal-article","created":{"date-parts":[[2016,4,4]],"date-time":"2016-04-04T13:01:06Z","timestamp":1459774866000},"page":"2340-2347","source":"Crossref","is-referenced-by-count":134,"title":["TSH\/IGF-1 Receptor Cross Talk in Graves' Ophthalmopathy Pathogenesis"],"prefix":"10.1210","volume":"101","author":[{"given":"Christine C.","family":"Krieger","sequence":"first","affiliation":[{"name":"Laboratory of Endocrinology and Receptor Biology (C.C.K., R.F.P., C.B., B.M.-S., S.N., M.C.G.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F.","family":"Place","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Receptor Biology (C.C.K., R.F.P., C.B., B.M.-S., S.N., M.C.G.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892"},{"name":"Nova Therapeutics LLC (R.F.P.), Pasadena, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Bevilacqua","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrinology and Receptor Biology (C.C.K., R.F.P., C.B., B.M.-S., S.N., M.C.G.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 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