title: Thyroid hormone export regulates cellular hormone content and response.
abstract: Actions of thyroid hormones (THs) are determined by intracellular free hormone concentration. Here we report that enhanced TH extrusion via a saturable, cold-sensitive mechanism lowers intracellular TH and causes TH resistance in hepatoma cells. Since these cells overexpress multidrug resistance P-glycoproteins and TH extrusion and resistance are blunted by verapamil, P-glycoproteins may mediate this resistance. Verapamil-inhibitable TH efflux was also found in primary hepatocytes, cardiocytes, and fibroblasts. These findings demonstrate that TH extrusion can modulate TH availability and action in mammalian cells.
authors.affiliation: Department of Medicine, University of California, San Francisco, California 94143-0540, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Ribeiro
authors.forename: R R
authors.initials: RR
authors.lastname: Cavalieri
authors.forename: N
authors.initials: N
authors.lastname: Lomri
authors.forename: C M
authors.initials: CM
authors.lastname: Rahmaoui
authors.forename: J D
authors.initials: JD
authors.lastname: Baxter
authors.forename: B F
authors.initials: BF
authors.lastname: Scharschmidt
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D013974:Thyroxine / Q000378:metabolism*; D014162:Transfection; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology; D014819:Vitellogenins / Q000235:genetics
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011988:Receptors, Thyroid Hormone; D011994:Recombinant Proteins; D014819:Vitellogenins; D014284:Triiodothyronine; D004958:Estradiol; D014700:Verapamil; D013974:Thyroxine