{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,2,15]],"date-time":"2023-02-15T05:23:00Z","timestamp":1676438580200},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1986,10]]},"abstract":"<jats:p>Abstract. The liver is a major site of conversion of thyroxine (T<jats:sub>4<\/jats:sub>) to the more active thyroid hormone 3,5,3'-triiodothyronine (T<jats:sub>3<\/jats:sub>). Hepatic T<jats:sub>4<\/jats:sub> to T<jats:sub>3<\/jats:sub> conversion is altered by a variety of pathological processes and pharmacological agents. We studied T<jats:sub>4<\/jats:sub> to T<jats:sub>3<\/jats:sub> conversion in glucuronyl transferase deficient homozygous Gunn rats because they have a hepatic enzyme abnormality which leads to hyperbilirubinaemia, and also because they have been reported to have alterations in thyroid hormone metabolism. An in vitro incubation system employing the 10 000 \u00d7 <jats:italic>g<\/jats:italic> supernatant of liver homogenate was used, and T<jats:sub>3<\/jats:sub> production was measured by radioimmunoassay. Experiments were done using substrate concentrations ranging from 0.56 to 20 \u03bc<jats:sc>m<\/jats:sc>, tissue protein in concentrations ranging from 0.625 to 20 mg and incubation times of 15 to 60 min. T<jats:sub>3<\/jats:sub> production by liver homogenates from homozygous Gunn rats in these studies ranged from 29 to 70% of that produced by liver homogenates from phenotypically normal heterozygous Gunn rats. The deficit in hepatic T<jats:sub>3<\/jats:sub> production by homozygous rats could not be overcome by increasing cofactor concentrations. After ultracentrifugation at 100 000 \u03bc <jats:italic>g<\/jats:italic>, T<jats:sub>4<\/jats:sub>-5'-deiodinase activity was found primarily in the 100 000 \u00d7 <jats:italic>g<\/jats:italic> sediment fraction. Homogygous rat liver 100 000 \u00d7 <jats:italic>g<\/jats:italic> sediment T<jats:sub>3<\/jats:sub> production was 55% of that of the heterozygous rat liver 100 000 \u00d7 <jats:italic>g<\/jats:italic> sediment. Liver cytosol from both homozygous and heterozygous rats inhibited microsomal T<jats:sub>4<\/jats:sub>-5'-deiodinase activity similarly. Addition of unconjugated bilirubin to liver homogenates resulted in reduction of T<jats:sub>3<\/jats:sub> production in livers from both homozygous and heterozygous rats. Thus the diminished capacity for hepatic conversion of T<jats:sub>4<\/jats:sub> to T<jats:sub>3<\/jats:sub> in homozygous Gunn rats may be due to inhibition of T<jats:sub>4<\/jats:sub>-5'-deiodinase activity by high endogenous levels of unconjugated bilirubin.<\/jats:p>","DOI":"10.1530\/acta.0.1130281","type":"journal-article","created":{"date-parts":[[2008,12,15]],"date-time":"2008-12-15T21:53:47Z","timestamp":1229378027000},"page":"281-288","update-policy":"http:\/\/dx.doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":2,"title":["Diminished hepatic triiodothyronine production in Gunn rats"],"prefix":"10.1093","volume":"113","author":[{"given":"J. R.","family":"Saltzman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. W.","family":"Clark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. D.","family":"Utiger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","container-title":["Acta Endocrinologica"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/113\/2\/acta_113_2_018.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/113\/2\/acta_113_2_018.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:27:54Z","timestamp":1676392074000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/113\/2\/281\/6764065"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1986,10]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/acta.0.1130281","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1986,10]]}}}