title: Xanthohumol, a prenylated chalcone from hops, modulates hepatic expression of genes involved in thyroid hormone distribution and metabolism.
abstract: In the present study, we analyzed the influence of xanthohumol (XN) on thyroid hormone (TH) distribution and metabolism in rats. A potent and selective competition of XN for thyroxine (T4) binding to transthyretin (IC(50)=1 microM at 1.7 nM [(125)I]T4) was found in human and rat sera in vitro. Female rats treated orally with XN showed increased hepatic expression of T4-binding globulin and decreased transthyretin and albumin. Thyrotropin levels and hepatic type 1 deiodinase activity were moderately increased. Northern blot analysis revealed diminished expression of liver sulfotransferase (Sult1a1) and uridine-diphosphate glucuronosyltransferase (Ugt1a1) after XN treatment. The transcript levels of constitutive androstane receptor (CAR), known to be involved in regulation of enzymes metabolizing hormones, drugs and xenobiotics, was lower in rats treated with >10 mg XN/kg body weight per day. Immunoblot analysis indicates reduced amounts of CAR protein. The phenobarbital-inducible cytochrome P450 mRNA level was decreased in rats treated with >10 mg XN/kg/day, in agreement with reduced CAR protein. Although only moderate changes in TH serum levels were observed, the XN-dependent altered expression of components involved in TH homeostasis might be important not only for hormone metabolism, but also for hepatic phase I and II elimination of drug metabolites and xenobiotics.
authors.affiliation: Institut für Experimentelle Endokrinologie & Endokrinologisches Forschungs-Centrum EnForCé, Charité Universitätsmedizin, Berlin, Germany. branislav.radovic@medunigraz.at
authors.forename: Branislav
authors.initials: B
authors.lastname: Radović
authors.forename: Ragna
authors.initials: R
authors.lastname: Hussong
authors.forename: Clarissa
authors.initials: C
authors.lastname: Gerhäuser
authors.forename: Walter
authors.initials: W
authors.lastname: Meinl
authors.forename: Norbert
authors.initials: N
authors.lastname: Frank
authors.forename: Hans
authors.initials: H
authors.lastname: Becker
authors.forename: Josef
authors.initials: J
authors.lastname: Köhrle
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D001711:Biotransformation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D035264:Flowers / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D027582:Humulus / Q000737:chemistry*; D007453:Iodide Peroxidase / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism; D011427:Propiophenones / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood / Q000378:metabolism; D056825:Thyroxine-Binding Globulin / Q000235:genetics / Q000378:metabolism
chemical_list: D005419:Flavonoids; D011228:Prealbumin; D011427:Propiophenones; D012333:RNA, Messenger; D013963:Thyroid Hormones; D056825:Thyroxine-Binding Globulin; C109812:iodothyronine deiodinase type I; D007453:Iodide Peroxidase; D013974:Thyroxine; C104536:xanthohumol