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Polychlorinated biphenyls suppress thyroid hormone-induced transactivation
Toshiharu Iwasaki1, Wataru Miyazaki, Akira Takeshita
1Department of Physiology, Gunma University School of Medicine, Maebashi, Gunma, Japan.
Biochemical and Biophysical Research Communications
|November 26, 2002
Summary
Very low doses of polychlorinated biphenyls (PCBs) disrupt thyroid hormone receptor (TR) activity, potentially harming central nervous system (CNS) development. These endocrine disruptors interfere with TR coactivator complex function, impacting thyroid hormone-mediated transcription.
Area of Science:
- Environmental Science
- Endocrinology
- Neuroscience
Background:
- Polychlorinated biphenyls (PCBs) are known endocrine-disrupting chemicals affecting multiple organs, including the central nervous system (CNS).
- Thyroid hormone (TH) plays a crucial role in growth and development, particularly within the CNS.
Purpose of the Study:
- To investigate the impact of PCBs on thyroid hormone (T3)-mediated gene transcription.
- To determine the specific mechanism by which PCBs interfere with thyroid hormone receptor (TR) function.
Main Methods:
- Transfection-based reporter assays were utilized to measure T3-induced transactivation.
- Various cell lines, including the brain-derived TE671 cell line, were used to assess PCB effects.
- The interaction between PCBs, TR, and coactivators (like SRC-1) was examined.
Main Results:
- A specific PCB (4(OH)-2',3,3',4',5'-pentachlorobiphenyl) suppressed T3-induced transactivation at extremely low concentrations (10(-10)M).
- Brain-derived TE671 cells exhibited significant suppression of TR activity by PCBs.
- PCBs interfered with the TR/coactivator (SRC-1) complex, rather than competing with T3 binding.
- PCBs did not affect glucocorticoid receptor-mediated transcription, indicating specificity.
Conclusions:
- Very low doses of PCBs can disrupt thyroid hormone receptor (TR)-mediated transcription.
- PCBs interfere with the TR/coactivator complex, potentially impairing normal development.
- These findings highlight the risk of PCBs to TH target organs, especially the CNS.
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