{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:19:20Z","timestamp":1790741960115,"version":"4.1.0"},"reference-count":0,"publisher":"Bioscientifica","issue":"2","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,5]]},"abstract":"<jats:p>\n                    Thyroid hormone receptor (TR) and liver X-receptor (LXR) are the master regulators of lipid metabolism. Remarkably, a mouse with a targeted deletion of both LXR\u03b1 and LXR\u03b2 is resistant to western diet-induced obesity, and exhibits ectopic liver expression of the thyroid hormone activating type 2 deiodinase (D2). We hypothesized that LXR\/retinoid X-receptor (RXR) signaling inhibits hepatic D2 expression, and studied this using a luciferase reporter containing the human\n                    <jats:italic>DIO2<\/jats:italic>\n                    (h\n                    <jats:italic>DIO2<\/jats:italic>\n                    ) promoter in HepG2 cells. Given that, in contrast to mammals, the chicken liver normally expresses D2, the chicken\n                    <jats:italic>DIO2<\/jats:italic>\n                    (c\n                    <jats:italic>DIO2<\/jats:italic>\n                    ) promoter was also studied. 22(R)-OH-cholesterol negatively regulated h\n                    <jats:italic>DIO2<\/jats:italic>\n                    in a dose-dependent manner (100\u200a\u03bcM, approximately twofold), while it failed to affect the c\n                    <jats:italic>DIO2<\/jats:italic>\n                    promoter. Truncations in the h\n                    <jats:italic>DIO2<\/jats:italic>\n                    promoter identified the region \u2212901 to \u2212584\u200abp as critical for negative regulation. We also investigated if 9-\n                    <jats:italic>cis<\/jats:italic>\n                    retinoic acid (9-\n                    <jats:italic>cis<\/jats:italic>\n                    RA), the ligand for the heterodimeric partner of TR and LXR, RXR, could regulate the h\n                    <jats:italic>DIO2<\/jats:italic>\n                    promoter. Notably, 9-\n                    <jats:italic>cis<\/jats:italic>\n                    RA repressed the h\n                    <jats:italic>DIO2<\/jats:italic>\n                    luciferase reporter (1\u200a\u03bcM, approximately fourfold) in a dose-dependent manner, while coexpression of an inactive mutant RXR abolished this effect. However, it is unlikely that RXR homodimers mediate the repression of h\n                    <jats:italic>DIO2<\/jats:italic>\n                    since mutagenesis of a DR-1 at \u2212506\u200abp did not interfere with 9-\n                    <jats:italic>cis<\/jats:italic>\n                    RA-mediated repression. Our data indicate that h\n                    <jats:italic>DIO2<\/jats:italic>\n                    transcription is negatively regulated by both 22(R)-OH-cholesterol and 9-\n                    <jats:italic>cis<\/jats:italic>\n                    RA, which is consistent with LXR\/RXR involvement.\n                    <jats:italic>In vivo<\/jats:italic>\n                    , the inhibition of D2-mediated tri-iodothyronine (T\n                    <jats:sub>3<\/jats:sub>\n                    ) production by cholesterol\/9-\n                    <jats:italic>cis<\/jats:italic>\n                    RA could function as a feedback loop, given that T\n                    <jats:sub>3<\/jats:sub>\n                    decreases hepatic cholesterol levels.\n                  <\/jats:p>","DOI":"10.1677\/joe-09-0448","type":"journal-article","created":{"date-parts":[[2010,2,22]],"date-time":"2010-02-22T21:36:22Z","timestamp":1266874582000},"page":"179-186","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":31,"title":["Regulation of thyroid hormone activation via the liver X-receptor\/retinoid X-receptor pathway"],"prefix":"10.1530","volume":"205","author":[{"given":"Marcelo A","family":"Christoffolete","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1rton","family":"Doleschall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e9ter","family":"Egri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"Liposits","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann Marie","family":"Zavacki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio C","family":"Bianco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bal\u00e1zs","family":"Gereben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","container-title":["Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/joe.bioscientifica.com\/view\/journals\/joe\/205\/2\/179.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/joe.bioscientifica.com\/downloadpdf\/journals\/joe\/205\/2\/179.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:55:02Z","timestamp":1784555702000},"score":1,"resource":{"primary":{"URL":"http:\/\/journals.bioscientifica.com\/joe\/article\/205\/2\/179-186\/21948"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,2,22]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1677\/joe-09-0448","relation":{},"ISSN":["0022-0795","1479-6805"],"issn-type":[{"value":"0022-0795","type":"print"},{"value":"1479-6805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,2,22]]}}}