{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:10:20Z","timestamp":1779149420345,"version":"3.51.4"},"reference-count":68,"publisher":"American Society for Clinical Investigation","issue":"16","license":[{"start":{"date-parts":[[2021,8,23]],"date-time":"2021-08-23T00:00:00Z","timestamp":1629676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["NIH RO1 DK98576"],"award-info":[{"award-number":["NIH RO1 DK98576"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,23]]},"abstract":"<jats:p>\n                    Thyroid hormone receptor \u03b2 (THRB) is posttranslationally modified by small ubiquitin-like modifier (SUMO). We generated a mouse model with a mutation that disrupted sumoylation at lysine 146 (K146Q) and resulted in desumoylated THRB as the predominant form in tissues. The THRB K146Q mutant mice had normal serum thyroxine (T4), markedly elevated serum thyrotropin-stimulating hormone (TSH; 81-fold above control), and enlargement of both the pituitary and the thyroid gland. The marked elevation in TSH, despite a normal serum T4, indicated blunted feedback regulation of TSH. The THRB K146Q mutation altered the recruitment of transcription factors to the\n                    <jats:italic>TSH<\/jats:italic>\n                    <jats:italic>\u03b2<\/jats:italic>\n                    gene promoter, compared with WT, in hyperthyroidism and hypothyroidism. Thyroid hormone content (T4, T3, and rT3) in the thyroid gland of the THRB K146Q mice was 10-fold lower (per gram tissue) than control, despite normal TSH bioactivity. The expression of thyroglobulin and dual oxidase 2 genes in the thyroid was reduced and associated with modifications of cAMP response element\u2013binding protein DNA binding and cofactor interactions in the presence of the desumoylated THRB. Therefore, thyroid hormone production had both TSH-dependent and TSH-independent components. We conclude that THRB sumoylation at K146 was required for normal TSH feedback regulation and TH synthesis in the thyroid gland, by a TSH-independent pathway.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.149425","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T12:02:30Z","timestamp":1625745750000},"source":"Crossref","is-referenced-by-count":13,"title":["Thyroid hormone receptor \u03b2 sumoylation is required for thyrotropin regulation and thyroid hormone production"],"prefix":"10.1172","volume":"6","author":[{"given":"Sujie","family":"Ke","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, and Department of Physiology, David Geffen School of Medicine, UCLA and VA Greater Los Angeles Healthcare System, Los Angeles, California, USA."},{"name":"Department of Endocrinology, Union Hospital, Fujian Medical University, Fuzhou, Fujian, 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