Different competition of thyroxine binding to transthyretin and thyroxine-binding globulin by hydroxy-PCBs, PCDDs and PCDFs.
In an earlier study several hydroxylated polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) competitively displaced [125I]thyroxine (T4) from transthyretin with different potencies. Transthyretin is the major T4 transport protein in plasma of rodents. In man, however, thyroxine-binding globulin transports most of the T4 in blood. In this study, hydroxylated PCBs, PCDDs and PCDFs were tested in an in vitro competitive binding assay, using purified human thyroxine-binding globulin and [125I]T4 as the displaceable radioligand. None of the tested hydroxylated PCBs, PCDDs and PCDFs inhibited [125I]T4 binding to thyroxine-binding globulin. In addition, some T4 derived compounds, e.g., tyrosine, mono-iodotyrosine, di-iodotyrosine and tri-iodophenol were tested on both transthyretin and thyroxine-binding globulin to investigate possible differences in structural characteristics determining T4 binding to thyroxine-binding globulin and transthyretin. The T4 derived compounds also did not inhibit [125I]T4 binding to thyroxine-binding globulin as tested in the in vitro assay. However, tri-iodophenol and to a lesser extent di-iodotyrosine inhibited [125I]T4-transthyretin binding. These results indicate a marked difference in T4 binding to thyroxine-binding globulin or transthyretin. The hydroxylated PCBs, PCDDs and PCDFs can inhibit T4 binding to transthyretin, but not to thyroxine-binding globulin, and thus may cause different effects in rodents and man.
Department of Toxicology, Agricultural University Wageningen, Netherlands.
M C
MC
Lans
C
C
Spiertz
A
A
Brouwer
J H
JH
Koeman
D001572:Benzofurans / Q000378:metabolism*; D001667:Binding, Competitive; D002850:Chromatography, Gel; D006801:Humans; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives* / Q000378:metabolism; D011228:Prealbumin / Q000378:metabolism*; D011485:Protein Binding; D013974:Thyroxine / Q000378:metabolism*; D013975:Thyroxine-Binding Proteins / Q000378:metabolism*
D001572:Benzofurans; D000072317:Polychlorinated Dibenzodioxins; D011228:Prealbumin; D013975:Thyroxine-Binding Proteins; C023614:dibenzofuran; D011078:Polychlorinated Biphenyls; D013974:Thyroxine