{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T16:43:00Z","timestamp":1793292180158,"version":"4.5.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["jme.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:p>\n                    Thyroid hormones increase hepatic sex hormone-binding globulin (SHBG) production, which is also regulated by hepatocyte nuclear factor-4\u03b1 (HNF-4\u03b1) in response to changes in the metabolic state of the liver. Since the human\n                    <jats:italic>SHBG<\/jats:italic>\n                    promoter lacks a typical thyroid hormone response element, and because thyroid hormones influence metabolic state, we set out to determine whether thyroid hormones mediate\n                    <jats:italic>SHBG<\/jats:italic>\n                    expression indirectly via changes in HNF-4\u03b1 levels in HepG2 human hepatoblastoma cells, and in the livers of transgenic mice that express a 4.3\u200akb human\n                    <jats:italic>SHBG<\/jats:italic>\n                    transgene under the control of its own 0.8\u200akb promoter sequence. Thyroid hormones (triiodothyronine (T\n                    <jats:sub>3<\/jats:sub>\n                    ) and thyroxine (T\n                    <jats:sub>4<\/jats:sub>\n                    )) increase SHBG accumulation in HepG2 cell culture medium over 5 days, and increase cellular SHBG mRNA levels. In addition, T\n                    <jats:sub>4<\/jats:sub>\n                    treatment of HepG2 cells for 5 days increased HNF-4\u03b1 mRNA and HNF-4\u03b1 levels in concert with decreased cellular palmitate levels. Plasma SHBG levels were also increased in mice expressing a human\n                    <jats:italic>SHBG<\/jats:italic>\n                    transgene after 5 days treatment with T\n                    <jats:sub>3<\/jats:sub>\n                    along with increased hepatic HNF-4\u03b1 levels. In HepG2 cells, the human\n                    <jats:italic>SHBG<\/jats:italic>\n                    promoter failed to respond acutely (within 24\u200ah) to T\n                    <jats:sub>4<\/jats:sub>\n                    treatment, but a 4-day pre-treatment with T\n                    <jats:sub>4<\/jats:sub>\n                    resulted in a robust response that was prevented by co-treatment with HNF-4\u03b1 siRNA, or by blocking the \u03b2-oxidation of palmitate through co-treatment with the carnitine palmitoyltransferase I inhibitor, etomoxir. These data lead us to conclude that thyroid hormones increase SHBG production indirectly by increasing\n                    <jats:italic>HNF-4<\/jats:italic>\n                    <jats:italic>\u03b1<\/jats:italic>\n                    gene expression, and by reducing cellular palmitate levels that further contribute to increased HNF-4\u03b1 levels in hepatocytes.\n                  <\/jats:p>","DOI":"10.1677\/jme-09-0025","type":"journal-article","created":{"date-parts":[[2009,3,31]],"date-time":"2009-03-31T21:10:37Z","timestamp":1238533837000},"page":"19-27","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":106,"title":["Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4\u03b1"],"prefix":"10.1530","volume":"43","author":[{"given":"David M","family":"Selva","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey L","family":"Hammond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Molecular Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/jme.bioscientifica.com\/view\/journals\/jme\/43\/1\/19.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/jme.bioscientifica.com\/downloadpdf\/journals\/jme\/43\/1\/19.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:52:16Z","timestamp":1784555536000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/jme\/article\/43\/1\/19-27\/12031"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3,31]]},"references-count":0,"journal-issue":{"issue":"1"},"URL":"https:\/\/doi.org\/10.1677\/jme-09-0025","relation":{},"ISSN":["0952-5041","1479-6813"],"issn-type":[{"value":"0952-5041","type":"print"},{"value":"1479-6813","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3,31]]}}}