{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:37:23Z","timestamp":1790271443514,"version":"4.1.0"},"reference-count":38,"publisher":"The Endocrine Society","issue":"9","license":[{"start":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T00:00:00Z","timestamp":1499731200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Context<\/jats:title><jats:p>Patients with resistance to thyroid hormone (TH) \u03b1 (RTH\u03b1) are characterized by growth retardation, macrocephaly, constipation, and abnormal thyroid function tests. In addition, almost all RTH\u03b1 patients have mild anemia, the pathogenesis of which is unknown. Animal studies suggest an important role for TH and TH receptor (TR)\u03b1 in erythropoiesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate whether a defect in TR\u03b1 affects the maturation of red blood cells in RTH\u03b1 patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design, Setting, and Patients<\/jats:title><jats:p>Cultures of primary human erythroid progenitor cells (HEPs), from peripheral blood of RTH\u03b1 patients (n = 11) harboring different inactivating mutations in TR\u03b1 (P398R, F397fs406X, C392X, R384H, A382fs388X, A263V, A263S), were compared with healthy controls (n = 11). During differentiation, erythroid cells become smaller, accumulate hemoglobin, and express different cell surface markers. We assessed cell number and cell size, and used cell staining and fluorescence-activated cell sorter analysis to monitor maturation at different time points.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After \u223c14 days of ex vivo expansion, both control and patient-derived progenitors differentiated spontaneously. However, RTH\u03b1-derived cells differentiated more slowly. During spontaneous differentiation, RTH\u03b1-derived HEPs were larger, more positive for c-Kit (a proliferation marker), and less positive for glycophorin A (a differentiation marker). The degree of abnormal spontaneous maturation of RTH\u03b1-derived progenitors did not correlate with severity of underlying TR\u03b1 defect. Both control and RTH\u03b1-derived progenitors responded similarly when differentiation was induced. T3 exposure accelerated differentiation of both control- and RTH\u03b1 patient\u2013derived HEPs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Inactivating mutations in human TR\u03b1 affect the balance between proliferation and differentiation of progenitor cells during erythropoiesis, which may contribute to the mild anemia seen in most RTH\u03b1 patients.<\/jats:p><\/jats:sec>","DOI":"10.1210\/jc.2017-00840","type":"journal-article","created":{"date-parts":[[2017,7,11]],"date-time":"2017-07-11T18:09:06Z","timestamp":1499796546000},"page":"3517-3525","source":"Crossref","is-referenced-by-count":24,"title":["Anemia in Patients With Resistance to Thyroid Hormone \u03b1: A Role for Thyroid Hormone Receptor \u03b1 in Human Erythropoiesis"],"prefix":"10.1210","volume":"102","author":[{"given":"Anja L M","family":"van Gucht","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Erasmus University Medical Center, 3000 Rotterdam, The 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