DIFFERENT COMPETITION OF THYROXINE-BINDING TO TRANSTHYRETIN AND THYROXINE-BINDING GLOBULIN BY HYDROXY-PCBS, PCDDS AND PCDFS

被引:144
作者
LANS, MC
SPIERTZ, C
BROUWER, A
KOEMAN, JH
机构
[1] Department of Toxicology, Agricultural University Wageningen, 6703 HE Wageningen
来源
EUROPEAN JOURNAL OF PHARMACOLOGY-ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY SECTION | 1994年 / 270卷 / 2-3期
关键词
PCB (POLYCHLORINATED BIPHENYL); PCDD (DIBENZO-P-DIOXIN); PCDF (DIBENZOFURAN); HYDROXYLATED METABOLITE; THYROXINE-BINDING GLOBULIN; TRANSTHYRETIN;
D O I
10.1016/0926-6917(94)90054-X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
In an earlier study several hydroxylated polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) competitively displaced [I-125]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 [I-125]T-4 as the displaceable radioligand. None of the tested hydroxylated PCBs, PCDDs and PCDFs inhibited [I-125]T, 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 [I-125]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 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.
引用
收藏
页码:129 / 136
页数:8
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