Thyroid hormone export regulates cellular hormone content and response.
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.
Ribeiro
R C
RC
Department of Medicine, University of California, San Francisco, California 94143-0540, USA.
Cavalieri
R R
RR
Lomri
N
N
Rahmaoui
C M
CM
Baxter
J D
JD
Scharschmidt
B F
BF
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
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