2004 Fiscal Year Final Research Report Summary
Analysis of endocrine-disrupting activities of environmental chemicals that associate with thyroid-hormone-binding proteins
| Project/Area Number |
13559001
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 展開研究 |
|---|
| Research Field |
広領域
|
|---|
| Research Institution | Shizuoka University |
|---|
Principal Investigator |
YAMAUCHI Kiyoshi Shizuoka University, Faculty of Science, Professor, 理学部, 教授 (50201827)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
ROBERT.D. Denver ミシガン大学, 生物学部, 助教授
DENVER Roberst J. The University of Michigan, Department of Biology, Associate Professor
|
|---|
| Project Period (FY) |
2001 – 2003
|
| Keywords | Environmental chemicals / Thyroid hormone / Receptor / Binding protein / Amphibian |
|---|
| Research Abstract |
We investigated the effects of phenolic and phenol compounds on 3,3',5-[^<125>I]triiodothyronine ([^<125>I]T_3) binding to purified Xenopus laevis transthyretin (xTTR) and to the ligand-binding domain of X. laevis thyroid hormone receptor β (xTR LBD), on T_3-induced metamorphosis in X. laevis tadpoles and on the induction of T_3-dependent reporter gene in a X. laevis cell line. Of the halogenated phenolic and phenol compounds tested, 3,3',5-trichlorobisphenol A and 2,4,6-triiodophenol, respectively, were the most potent competitors of [^<125>I]T_3 binding to both xTTR and xTR LBD. Most of the halogenated compounds had stronger interactions with xTTR than with xTR LBD. Generally, chlorinated derivatives with a greater degree of chlorination were more efficient competitors of T_3 binding to xTTR and xTR LBD. Structures with a halogen in either ortho positions or in both ortho positions, with respect to the hydroxy group, were more efficient competitors. 3,3',5-Trichlorobisphenol A and 2,4,6-triiodophenol acted as T_3 antagonists in the X laevis tadpole metamorphosis assay. Interestingly, o-t-butylphenol and 2-isopropylphenol, for which xTTR and xTR LBD had weak or no significant affinity, showed T_3 antagonist activity in the metamorphosis assay. T_3 antagonist activities of all these chemicals except for o-t-butylphenol were verified by T_3-dependent reporter gene assay. Our results suggest that some phenolic and phenol compounds target the process of T_3 binding to xTTR and xTR and/or an unknown process, and that they interfere with the intracellular T_3 signaling pathway.
|
