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 (PC Bs), dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) competitively displaced [I-125]thyroxine (T-4) from transthyretin with different po tencies. Transthyretin is the major T-4 transport protein in plasma of rodents. In man, however, thyroxine-binding globulin transports most of the T-4 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 [I-125]T-4 as the displaceable ra dioligand. None of the tested hydroxylated PCBs, PCDDs and PCDFs inhib ited [I-125]T, binding to thyroxine-binding globulin. In addition, som e T-4 derived compounds, e.g., tyrosine, mono-iodotyrosine, di-iodotyr osine and tri-iodophenol were tested on both transthyretin and thyroxi ne-binding globulin to investigate possible differences in structural characteristics determining T-4 binding to thyroxine-binding globulin and transthyretin. The T-4 derived compounds also did not inhibit [I-1 25]T-4 binding to thyroxine-binding globulin as tested in the in vitro assay. However, tri-iodophenol and to a lesser extent di-iodotyrosine inhibited [I-125]T-4-transthyretin binding. These results indicate a marked difference in T-4 binding to thyroxine-binding globulin or tran sthyretin. The hydroxylated PCBs, PCDDs and PCDFs can inhibit T-4 bind ing to transthyretin, but not to thyroxine-binding globulin, and thus may cause different effects in rodents and man.