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J.Health Sci., 49(2), 99-104, 2003
Detection of Thyroid Hormone Receptor-Binding Activities of Chemicals Using a Yeast
Two-Hybrid Assay
Yoko Kitagawa,*, a Satoshi
Takatori,a Hajime
Oda,a Jun-ichi
Nishikawa,b Tsutomu
Nishihara,b Hiroyuki
Nakazawa,c and Shinjiro
Horia
aOsaka Prefectural Institute of Public Health, 3-69, 1-chome, Nakamichi, Higashinari-ku, Osaka 537-0025, Japan,
bGraduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan, and
cFaculty of Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan
The adverse effects of chemicals exerted
via estrogen receptors (ER) and androgen receptors (AR) have
been studied extensively in recent years. However, those occurring
via thyroid hormone receptors (TR) have not
been studied enough. We examined the TR-binding activities of thyronine derivatives and alkylphenol
derivatives (bisphenol A, parabens and antioxidants with
o-t-butylphenol residue) using a yeast two-hybrid assay. In
this assay system, the TR-binding activity of
3,5,3'-triiodo-L-thyronine (T3) was detectable at concentrations as
low as 3.0 × 10-8 M and reached a plateau at 1.0 ×
10-6 M. The concentration of
T3 producing 10% of the activity stimulated at 1.0 ×
10-6 M (10% relative effective concentration,
REC10) was 2.1 ×
10-8 M.
3,5,3',5'-tetraiodo-L-thyronine
(T4), 3,3',5'-triiodo-L-thyronine
(rT3) and 3, 5-diiodo-L-thyronine
(T2) also exhibited TR-binding activities. The
REC10 values of these chemicals were 4.2 ×
10-8, 5.0 ×
10-7 and 1.0 ×
10-5 M, respectively. o-Isopropylphenol and
o-t-butylphenol exhibited TR-binding activities with
REC10 values of 3.1 ×
10-4 and 4.8 ×
10-5 M, respectively, whereas
t-butylbenzene, isopropylbenzene and the other chemicals tested had no
detectable TR-bindng activity. These results suggest that a phenolic hydroxyl group and the
ortho-substituents may play important roles in the TR-binding activities of these chemicals. This assay system will be a useful tool for
screening the TR-binding activities of chemicals.
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