{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T22:45:14Z","timestamp":1772577914859,"version":"3.50.1"},"reference-count":46,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-133557"],"award-info":[{"award-number":["MOP-133557"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["2015-05178"],"award-info":[{"award-number":["2015-05178"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Loss of function mutations in IGSF1\/Igsf1 cause central hypothyroidism. Igsf1 knockout mice have reduced pituitary thyrotropin-releasing hormone receptor, Trhr, expression, perhaps contributing to the phenotype. Because thyroid hormones negatively regulate Trhr, we hypothesized that IGSF1 might affect thyroid hormone availability in pituitary thyrotropes. Consistent with this idea, IGSF1 coimmunoprecipitated with the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) in transfected cells. This association was impaired with IGSF1 bearing patient-derived mutations. Wild-type IGSF1 did not, however, alter MCT8-mediated thyroid hormone import into heterologous cells. IGSF1 and MCT8 are both expressed in the apical membrane of the choroid plexus. However, MCT8 protein levels and localization in the choroid plexus were unaltered in Igsf1 knockout mice, ruling out a necessary chaperone function for IGSF1. MCT8 expression was low in the pituitary and was similarly unaffected in Igsf1 knockouts. We next assessed whether IGSF1 affects thyroid hormone transport or action, by MCT8 or otherwise, in vivo. To this end, we treated hypothyroid wild-type and Igsf1 knockout mice with exogenous thyroid hormones. T4 and T3 inhibited TSH release and regulated pituitary and forebrain gene expression similarly in both genotypes. Interestingly, pituitary TSH beta subunit (Tshb) expression was consistently reduced in Igsf1 knockouts relative to wild-type regardless of experimental condition, whereas Trhr was more variably affected. Although IGSF1 and MCT8 can interact in heterologous cells, the physiological relevance of their association is not clear. Nevertheless, the results suggest that IGSF1 loss can impair TSH production independently of alterations in TRHR levels or thyroid hormone action.<\/jats:p>","DOI":"10.1210\/endocr\/bqac092","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T11:33:40Z","timestamp":1655379220000},"source":"Crossref","is-referenced-by-count":6,"title":["IGSF1 Deficiency Leads to Reduced TSH Production Independent of Alterations in Thyroid Hormone Action in Male Mice"],"prefix":"10.1210","volume":"163","author":[{"given":"Emilie","family":"Br\u00fbl\u00e9","sequence":"first","affiliation":[{"name":"Department of Anatomy and Cell Biology, McGill University , Montreal H3G 1Y6 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanya L","family":"Silander","sequence":"additional","affiliation":[{"name":"Integrated Program in Neuroscience, McGill University , Montreal H3G 1Y6 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, McGill University , Montreal H3G 1Y6 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, McGill University , Montreal H3G 1Y6 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Beata","family":"Bak","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, McGill University , Montreal H3G 1Y6 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6879-7392","authenticated-orcid":false,"given":"Stefan","family":"Groeneweg","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Erasmus Medical Center, Academic Center for Thyroid Diseases , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5365-5586","authenticated-orcid":false,"given":"Daniel J","family":"Bernard","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, McGill University , Montreal H3G 1Y6 , Canada"},{"name":"Integrated Program in Neuroscience, McGill University , Montreal H3G 1Y6 , Canada"},{"name":"Department of Pharmacology and Therapeutics, McGill University , Montreal H3G 1Y6 , Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"issue":"12","key":"2022070616263601700_CIT0001","doi-asserted-by":"crossref","first-page":"4942","DOI":"10.1210\/jc.2013-2743","article-title":"van Trotsenburg AS. 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