Different competition of thyroxine binding to transthyretin and thyroxine-binding globulin by hydroxy-PCBs, PCDDs and PCDFs

Abstract

In an earlier study several hydroxylated polychlorinated biphenyls (PCBs), dibenzo- p-dioxins (PCDDs) and dibenzofurans (PCDFs) competitively displaced [ 125I]thyroxine (T 4) from transthyretin with different potencies. 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 [ 125I]T 4 as the displaceable radioligand. None of the tested hydroxylated PCBs, PCDDs and PCDFs inhibited [ 125I]T 4 binding to thyroxine-binding globulin. In addition, some T 4 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 T 4 binding to thyroxine-binding globulin and transthyretin. The T 4 derived compounds also did not inhibit [ 125I]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 [ 125I]T 4-transthyretin binding. These results indicate a marked difference in T 4 binding to thyroxine-binding globulin,or transthyretin. The hydroxylated PCBs, PCDDs and PCDFs can inhibit T 4 binding to transthyretin, but not to thyroxine-binding globulin, and thus may cause different effects in rodents and man.