{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:46:24Z","timestamp":1784547984244,"version":"3.55.0"},"reference-count":48,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Thyroid hormone (TH) deficiency has been associated with increased cholesterol gallstone prevalence. Hypothyroidism impacts hepatic lipid homeostasis, biliary secretion, gallbladder motility, and gallstone (LITH) gene expression, all potential factors contributing to cholesterol gallstone disease (CGD). However, how TH deficiency may lead to gallstone formation is still poorly understood. Therefore, we performed molecular studies in a CGD mouse model under lithogenic conditions and modulation of TH status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Male, three-month-old C57BL\/6 mice were randomly divided into a control (euthyroid) group, a hypothyroid (hypo) group, a gallstone (litho) group, and a gallstone+hypothyroid (litho+hypo) group and were treated for 2, 4, and 6 weeks (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u20098\/treatment period). Gallstone prevalence, biliary composition and cholesterol crystals, hepatic expression of genes participating in cholesterol, bile acid (BA), and phosphatidylcholine synthesis (\n                      <jats:italic toggle=\"yes\">Hmgcr<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Cyp7a1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Pcyt1a<\/jats:italic>\n                      ), and canalicular transport (\n                      <jats:italic toggle=\"yes\">Abcg5<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Bsep<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">Abcb4<\/jats:italic>\n                      ) were investigated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Increased cholesterol gallstone prevalence was observed in hypothyroid mice under lithogenic diet after 4 and 6 weeks of treatment (4 weeks: 25% vs. 0%; 6 weeks: 75% vs. 37.5%). Interestingly, neither the composition of the three main biliary components, cholesterol, BAs, and phosphatidylcholine, nor the hepatic expression of genes involved in synthesis and transport could explain the differences in cholesterol gallstone formation in the mice. However, TH deficiency resulted in significantly increased hydrophobicity of primary BAs in bile. Furthermore, downregulation of hepatic sulfonation enzymes\n                      <jats:italic toggle=\"yes\">Papss2<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Sult2a8<\/jats:italic>\n                      as well as diminished biliary BA sulfate concentrations in mice were observed under hypothyroid conditions all contributing to a lithogenic biliary milieu as evidenced by microscopic cholesterol crystals and macroscopic gallstone formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>We describe a novel pathogenic link between TH deficiency and CGD and suggest that the increased hydrophobic character of biliary BAs due to the diminished expression of hepatic detoxification enzymes promotes cholesterol crystal precipitation and enhances cholesterol gallstone formation in the bile of hypothyroid mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2020.0636","type":"journal-article","created":{"date-parts":[[2020,11,24]],"date-time":"2020-11-24T08:39:16Z","timestamp":1606207156000},"page":"973-984","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Hypothyroidism Increases Cholesterol Gallstone Prevalence in Mice by Elevated Hydrophobicity of Primary Bile Acids"],"prefix":"10.1177","volume":"31","author":[{"given":"Irina","family":"Kube","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism and Clinical Chemistry, Division of Laboratory Research, University of Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca Bartolomeo","family":"Tardio","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism and Clinical Chemistry, Division of Laboratory Research, University of Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology and University of T\u00fcbingen, Stuttgart, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Ghallab","sequence":"additional","affiliation":[{"name":"Department of Toxicology\/Systems Toxicology, Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany."},{"name":"Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, South Valley University, Qena, Egypt."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan G.","family":"Hengstler","sequence":"additional","affiliation":[{"name":"Department of Toxicology\/Systems Toxicology, Leibniz Research Centre for Working Environment and Human Factors, Dortmund, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dagmar","family":"F\u00fchrer","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism and Clinical Chemistry, Division of Laboratory Research, University of Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Zwanziger","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism and Clinical Chemistry, Division of Laboratory Research, University of Duisburg-Essen, Essen, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0096(199901)27:1<1::AID-JCU1>3.0.CO;2-H"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69044-2"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-020798"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.14.5282"},{"key":"e_1_3_5_6_2","first-page":"919","article-title":"Association between common bile duct stones and treated hypothyroidism","volume":"47","author":"Inkinen J","year":"2000","unstructured":"Inkinen J, , Sand J, , Nordback I. 2000. 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