{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:50:56Z","timestamp":1790063456091,"version":"4.0.1"},"reference-count":26,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>TSH is the most important biomarker in the interpretation of thyroid function in man. Its levels are determined by circulating thyroid hormone (TH) levels that feed back centrally to regulate the expression of the subunits that comprise TSH from the pituitary. The nuclear corepressor 1 (NCoR1), is a critical coregulator of the TH receptor (TR) isoforms. It has been established to play a major role in the control of TSH secretion, because mice that express a mutant NCoR1 allele (NCoR\u0394ID) that cannot interact with the TR have normal TSH levels despite low circulating TH levels. To determine how NCoR1 controls TSH secretion, we first developed a mouse model that allowed for induction of NCoR\u0394ID expression postnatally to rule out a developmental effect of NCoR1. Expression of NCoR\u0394ID postnatally led to a drop in TH levels without a compensatory rise in TSH production, indicating that NCoR1 acutely controls both TH production and feedback regulation of TSH. To demonstrate that this was a cell autonomous function of NCoR1, we expressed NCoR\u0394ID in the pituitary using a Cre driven by the glycoprotein \u03b1-subunit promoter (P-\u0394ID mice). Importantly, P-\u0394ID mice have low TH levels with decreased TSH production. Additionally, the rise in TSH during hypothyroidism is blunted in P-\u0394ID mice. Thus, NCoR1 plays a critical role in TH-mediated regulation of TSH in the pituitary by regulating the repressive function of the TR. Furthermore, these studies suggest that endogenous NCoR1 levels in the pituitary could establish the set point of TSH secretion.<\/jats:p>","DOI":"10.1210\/en.2012-1504","type":"journal-article","created":{"date-parts":[[2012,9,21]],"date-time":"2012-09-21T17:45:03Z","timestamp":1348249503000},"page":"5049-5057","source":"Crossref","is-referenced-by-count":32,"title":["The Thyroid Axis Is Regulated by NCoR1 via Its Actions in the Pituitary"],"prefix":"10.1210","volume":"153","author":[{"given":"Ricardo H.","family":"Costa-e-Sousa","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism (R.H.C.S., I.A., F.Y., A.N.H.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215"},{"name":"CAPES Foundation (R.H.C.S.), Ministry of Education of Brazil, Bras\u00edlia, DF, 70040-020 Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inna","family":"Astapova","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism (R.H.C.S., I.A., F.Y., A.N.H.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Ye","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism (R.H.C.S., I.A., F.Y., A.N.H.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredric E.","family":"Wondisford","sequence":"first","affiliation":[{"name":"Department of Pediatrics and Medicine (F.E.W.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony N.","family":"Hollenberg","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Diabetes and Metabolism (R.H.C.S., I.A., F.Y., A.N.H.), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02215"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612184243900_B1","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1210\/en.2008-1795","article-title":"Minireview: Thyrotropin-releasing hormone and the thyroid hormone feedback mechanism.","volume":"150","author":"Chiamolera","year":"2009","journal-title":"Endocrinology"},{"key":"2020071612184243900_B2","doi-asserted-by":"crossref","first-page":"14840","DOI":"10.1016\/S0021-9258(18)63777-9","article-title":"Thyroid hormone regulates the mouse thyrotropin \u03b2-subunit promoter in transfected primary thyrotropes.","volume":"264","author":"Wood","year":"1989","journal-title":"J Biol Chem"},{"key":"2020071612184243900_B3","doi-asserted-by":"crossref","first-page":"24927","DOI":"10.1074\/jbc.272.40.24927","article-title":"A unique role of the \u03b2-2 thyroid hormone receptor isoform in negative regulation by thyroid hormone. Mapping of a novel amino-terminal domain important for ligand-independent activation.","volume":"272","author":"Langlois","year":"1997","journal-title":"J Biol Chem"},{"key":"2020071612184243900_B4","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1172\/JCI5205","article-title":"Novel insight from transgenic mice into thyroid hormone resistance and the regulation of thyrotropin.","volume":"103","author":"Abel","year":"1999","journal-title":"J Clin Invest"},{"key":"2020071612184243900_B5","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1172\/JCI10858","article-title":"Critical role for thyroid hormone receptor \u03b22 in the regulation of paraventricular thyrotropin-releasing hormone neurons.","volume":"107","author":"Abel","year":"2001","journal-title":"J Clin Invest"},{"key":"2020071612184243900_B6","doi-asserted-by":"crossref","first-page":"1529","DOI":"10.1210\/me.2005-0014","article-title":"Pituitary resistance to thyroid hormone syndrome is associated with T3 receptor mutants that selectively impair beta2 isoform function.","volume":"19","author":"Wan","year":"2005","journal-title":"Mol Endocrinol"},{"key":"2020071612184243900_B7","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1210\/en.2009-0976","article-title":"The thyrotropin-releasing hormone gene is regulated by thyroid hormone at the level of transcription in vivo.","volume":"151","author":"Sugrue","year":"2010","journal-title":"Endocrinology"},{"key":"2020071612184243900_B8","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nrg2736","article-title":"Deconstructing repression: evolving models of co-repressor action.","volume":"11","author":"Perissi","year":"2010","journal-title":"Nat Rev Genet"},{"key":"2020071612184243900_B9","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1210\/er.2009-0007","article-title":"Molecular aspects of thyroid hormone actions.","volume":"31","author":"Cheng","year":"2010","journal-title":"Endocr Rev"},{"key":"2020071612184243900_B10","doi-asserted-by":"crossref","first-page":"19544","DOI":"10.1073\/pnas.0804604105","article-title":"The nuclear corepressor, NCoR, regulates thyroid hormone action in vivo.","volume":"105","author":"Astapova","year":"2008","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612184243900_B11","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1210\/me.2010-0462","article-title":"The nuclear receptor corepressor (NCoR) controls thyroid hormone sensitivity and the set point of the hypothalamic-pituitary-thyroid axis.","volume":"25","author":"Astapova","year":"2011","journal-title":"Mol Endocrinol"},{"key":"2020071612184243900_B12","doi-asserted-by":"crossref","first-page":"3412","DOI":"10.1073\/pnas.1017707108","article-title":"Corepressor SMRT promotes oxidative phosphorylation in adipose tissue and protects against diet-induced obesity and insulin resistance.","volume":"108","author":"Fang","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612184243900_B13","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1038\/nm.2450","article-title":"Thyroid hormone receptor repression is linked to type I pneumocyte-associated respiratory distress syndrome.","volume":"17","author":"Pei","year":"2011","journal-title":"Nat Med"},{"key":"2020071612184243900_B14","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1095\/biolreprod.108.075259","article-title":"Impaired estrogen feedback and infertility in female mice with pituitary-specific deletion of estrogen receptor \u03b1 (ESR1).","volume":"81","author":"Singh","year":"2009","journal-title":"Biol Reprod"},{"key":"2020071612184243900_B15","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.stem.2007.03.002","article-title":"Deletion of the developmentally essential gene ATR in adult mice leads to age-related phenotypes and stem cell loss.","volume":"1","author":"Ruzankina","year":"2007","journal-title":"Cell Stem Cell"},{"key":"2020071612184243900_B16","doi-asserted-by":"crossref","first-page":"44988","DOI":"10.1074\/jbc.M111.291625","article-title":"Alternative mRNA splicing of corepressors generates variants that play opposing roles in adipocyte differentiation.","volume":"286","author":"Goodson","year":"2011","journal-title":"J Biol Chem"},{"key":"2020071612184243900_B17","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1210\/me.2004-0017","article-title":"Generation of thyrotropin-releasing hormone receptor 1-deficient mice as an animal model of central hypothyroidism.","volume":"18","author":"Rabeler","year":"2004","journal-title":"Mol Endocrinol"},{"key":"2020071612184243900_B18","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1038\/npp.2008.217","article-title":"TRH-receptor-type-2-deficient mice are euthyroid and exhibit increased depression and reduced anxiety phenotypes.","volume":"34","author":"Sun","year":"2009","journal-title":"Neuropsychopharmacology"},{"key":"2020071612184243900_B19","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1210\/me.2005-0115","article-title":"MED220\/thyroid receptor-associated protein 220 functions as a transcriptional coactivator with Pit-1 and GATA-2 on the thyrotropin-\u03b2 promoter in thyrotropes.","volume":"20","author":"Gordon","year":"2006","journal-title":"Mol Endocrinol"},{"key":"2020071612184243900_B20","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1093\/emboj\/18.7.1900","article-title":"Mice deficient in the steroid receptor co-activator 1 (SRC-1) are resistant to thyroid hormone.","volume":"18","author":"Weiss","year":"1999","journal-title":"EMBO J"},{"key":"2020071612184243900_B21","doi-asserted-by":"crossref","first-page":"2517","DOI":"10.1172\/JCI24109","article-title":"Negative regulation by thyroid hormone receptor requires an intact coactivator-binding surface.","volume":"115","author":"Ortiga-Carvalho","year":"2005","journal-title":"J Clin Invest"},{"key":"2020071612184243900_B22","doi-asserted-by":"crossref","first-page":"17462","DOI":"10.1073\/pnas.1107474108","article-title":"Resistance to thyroid hormone is modulated in vivo by the nuclear receptor corepressor (NCOR1).","volume":"108","author":"Fozzatti","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071612184243900_B23","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1172\/JCI109222","article-title":"Bihormonal regulation of the thyrotropin-releasing hormone receptor in mouse pituitary thyrotropic tumor cells in culture.","volume":"62","author":"Gershengorn","year":"1978","journal-title":"J Clin Invest"},{"key":"2020071612184243900_B24","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1210\/endo-110-5-1725","article-title":"Regulation of thyrotropin-releasing hormone receptors and responses by l-triiodothyronine in dispersed rat pituitary cell cultures.","volume":"110","author":"Hinkle","year":"1982","journal-title":"Endocrinology"},{"key":"2020071612184243900_B25","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/0006-291X(92)91202-2","article-title":"Differential regulation of thyrotropin-releasing hormone receptor mRNA levels by thyroid hormone in vivo and in vitro (GH3 cells).","volume":"184","author":"Yamada","year":"1992","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071612184243900_B26","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1210\/me.2010-0388","article-title":"PITX2 AND PITX1 regulate thyrotroph function and response to hypothyroidism.","volume":"25","author":"Castinetti","year":"2011","journal-title":"Mol Endocrinol"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/153\/10\/5049\/10388796\/endo5049.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/153\/10\/5049\/10388796\/endo5049.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,1,29]],"date-time":"2022-01-29T13:21:54Z","timestamp":1643462514000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/153\/10\/5049\/2424535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,10,1]]},"references-count":26,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2012,10,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2012-1504","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,10,1]]}}}