Department of Biology, Faculty of Science, Shizuoka University, Shizuoka 422-8529, Japan
1 To whom correspondence should be addressed at Department of Biology, Faculty of Science, Shizuoka University, 836 Ohya, Shizuoka 422-8529, Japan. Fax: +81 54 238 0986. E-mail: sbkyama{at}ipc.shizuoka.ac.jp.
Received August 27, 2004; accepted November 19, 2004
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Key Words: thyroid hormone; transthyretin; thyroid hormone receptor; halogenated phenolic compounds; thyroid disrupting chemicals; metamorphosis; Xenopus laevis.
![]() |
INTRODUCTION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
THs are important hormones of brain development, intelligence, and behavior in higher vertebrates (Porterfield, 1994; Zoeller et al., 2002
) and postembryonic development in lower vertebrates (Dickhoff et al., 1990
). However, there have been few reports concerning the molecular mechanisms of thyroid system disruption by EDCs. Of the EDCs, a number of organohalogen compounds are known to interfere with the thyroid system (Brucker-Davis, 1998
). Possible sites that the organohalogens target in the thyroid system include the thyroid gland (Collins et al., 1977
), the plasma TH binding protein, transthyretin (TTR) (Brouwer et al., 1998
), and TH metabolism (Byrne et al., 1987
). The disruption of the thyroid system by EDCs is characterized by the fact that there are few chemicals that competitively interact with 3,3',5-L-triiodothyronine (T3) binding to TH receptor (TR) (Cheek et al., 1999b
; Ishihara et al., 2003b
). This is in contrast to the steroid system (Matthews et al., 2000
), suggesting that thyroid system processes other than T3 binding to TR are targeted by EDCs, although this assumption is mainly based on in vitro studies (Cheek et al., 1999b
; Gauger et al., 2004
; Ishihara et al., 2003a
,b
; Yamauchi et al., 2003
). Recently, chlorinated derivatives of bisphenol A were detected at the concentrations of 108 M in wastewater from paper recycling plants in Japan (Fukazawa et al., 2001
). Of the chlorinated derivatives, trichlorobisphenol A and tetrachlorobisphenol A, structurally resemble T3 and L-thyroxine (T4), respectively. Therefore, it is likely that they interfere with the thyroid system.
To determine which thyroid system process is targeted by EDCs in vitro, the experimental animal model Xenopus laevis may provide the most insight. As X. laevis tadpoles are water-living animals (all of its life stages occur in water) and have thin and permeable body skin, they may be particularly sensitive to a number of EDCs present in water. X. laevis is widely used as a laboratory animal and its development and gene expression are well characterized. For these reasons, X. laevis has been approved as an experimental model for evaluating the effects of EDCs in amphibians by the Organization for Economic Cooperation and Development (OECD). As amphibian metamorphosis is obligatorily controlled by THs, amphibian tadpoles are a good model animal for understanding the molecular mechanism by which EDCs disrupt the thyroid system.
In the present study, we investigated the effects of phenolic and phenol compounds, including chlorinated and iodinated compounds, on the X. laevis thyroid system in vitrocompetitive interactions of the chemicals with 125I-T3 binding to X. laevis TTR (xTTR) and the ligand-binding domain of X.laevis TR (xTR LBD)and in vivoamphibian metamorphosis and T3-dependent gene reporter assays. The potent competitors detected in the in vitro study exhibited a T3-antagonist activity in the in vivo assay; however, some chemicals with almost no interaction with TR in the in vitro study also exhibited a T3-antagonist activity in the in vivo study.
![]() |
MATERIALS AND METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
All chemicals tested as EDCs were dissolved in dimethylsulfoxide to a concentration of 10 mM. These chemicals were diluted with an appropriate buffer to give less than 0.4% (v/v) solvent. A control assay without the test chemicals was performed in the presence of the solvent alone and at less than 0.4% (v/v). The solvent did not affect the competitive 125I-T3 binding assays, the metamorphosis assay nor the gene reporter assay described below.
Preparation of recombinant xTTR and xTR LBD. Recombinant xTTR and glutathione-S-transferease (GST) fused xTR LBD were expressed in Escherichia coli BL21 and purified from the bacterial extracts by affinity column chromatography, human retinol-binding protein coupled to Sepharose 4B (Larsson et al., 1985), and glutathione coupled to Sepharose 4B (Amersham Pharmacia Biotech), respectively, as described previously (Yamauchi et al., 2002
). They were stored in 10% glycerol at 85°C for later use. Protein concentration was determined by the dye-binding method using bovine
-globulin as the standard (Bradford, 1976
).
125I-T3 binding assays using TTR (TTR assay) and the TR LBD (TR assay). xTTR (300 ng/tube) was incubated with 0.1 nM 125I-T3 in 250 µl of 20 mM Tris-HCl, pH 7.5, 93 mM NaCl, and 1 mM CaCl2 in the presence or absence of 5 µM unlabeled T3 for 1.0 h at 4°C. GST-xTR LBD fusion protein (54 ng/tube) was incubated with 0.1 nM 125I-T3 in 250 µl of 10 mM Tris-HCl, pH 7.5, 1.5 mM EDTA, 1 mM dithiothreitol and 10% (v/v) glycerol in the presence or absence of 1 µM unlabeled T3 for 1.5 h at 4°C. Competitive 125I-T3 binding was performed with solvent only or increasing concentrations of the unlabeled test chemical, as described previously (Yamauchi et al., 2000). For the TTR assay, protein-bound 125I-T3 was separated from free 125I-T3 by the polyethylene glycol method (Yamauchi et al., 1993
). For the TR assay, the Dowex method (Lennon, 1992
; Lennon et al., 1980
) separated bound 125I-T3 from free 125I-T3. Radioactivity was measured in a gamma counter (Auto Well Gamma System ARC-2000, Aloka, Japan). The amount of 125I-T3 bound nonspecifically was derived from the radioactivity of samples incubated with excess unlabeled T3. The nonspecific binding value was subtracted from the amount of total bound 125I-T3 to give the value of specifically bound 125I-T3.
Metamorphosis assay. X. laevis tadpoles were purchased from Akita Xenopus Co. (Ibaraki, Japan). Tadpoles were staged according to Nieuwkoop and Faber; NF (1975). They were maintained under natural lighting conditions in a 20-l glass aquarium containing dechlorinated tap water and fed dried food commercially available for the fish Medaka (Kyorin Co., Himeji, Japan) once a week. Before starting experiments, test animals were acclimatized to laboratory conditions (2526°C) for 24 h. During the acclimatization and exposure periods, tadpoles were not fed. Five tadpoles in NF stages 5253 were transferred into a 1-l glass beaker containing 0.5 l of FETAX buffer (625 mg NaCl, 96 mg NaHCO3, 30 mg KCl, 15 mg CaCl2, 60 mg CaSO4.2H2O, and 75 mg MgSO4.7H2O per l distilled water, pH 7.7) (Dumont et al., 1983
). The FETAX buffer contained dimethylsulfoxide, T3 in dimethylsulfoxide, or T3 and each chemical in dimethylsulfoxide. Chemical applications were renewed every other day by changing the above FETAX buffer. Final dimethylsulfoxide concentrations were less than 0.02% in the chemical-exposed and control groups. Fresh NANOpure ultrapure water (Barnstead International, Dubuque, IA) was used for preparing the FETAX buffer. During the experiments, tadpoles were anesthetized in 0.02% 3-aminobenzoic acid ethyl ester (Sigma) and photographed under a stereomicroscope (type SZ-PT, Olympus, Japan) to measure body length, tail length, interocular distance, forelimb length, and hindlimb length. After 5 or 7 days, all living tadpoles were frozen in liquid nitrogen and then stored at 80°C until RNA preparation. Each experiment was repeated at least three times using tadpoles derived from different sets of adults.
Real-time polymerase chain reaction. Total RNA was extracted from the frozen tadpoles using the LiCl-urea procedure (Auffray and Rougeon, 1980). RNA (510 µg per lane) was electrophoresed in a 1% agarose gel containing 2.6 M formaldehyde. After visualizing 28S and 18S rRNAs by ethidium bromide staining to check the integrity of the RNA samples and equal loading, amounts of specific RNA species were estimated by real-time polymerase chain reaction (PCR) using SYBR Green Master Mix and ABI Prism 7000 (Applied Biosystems, Foster City, CA) after the RNA samples were treated with reverse transcriptase (TaqMan Reverese Transcription Reagents, Applied Biosystems). Each PCR was run in duplicate to control for PCR variation. The thermocycler program included a step of denaturation at 95°C (10 min), and 40 cycles of 95°C (15 sec), 60°C (1 min), and 50°C (2 min). The endpoint used in real-time PCR quantification, Ct, was defined as the PCR cycle number that crosses an arbitrarily placed signal threshold and is a function of the amount of target DNA present in the starting material. Quantification was determined by applying the 2Ct formula and calculating the average of the two values obtained for each sample. Eligibility of this formula was verified using a mixture of X. laevis cDNAs containing the xTRß cDNA at three different concentrations (1:50:250). To standardize each experiment, the amount of xTRß transcript was divided by the amount of glyceraldehyde dehydrogenase (GAPDH) RNA in the same samples. Primer sequences used were as follows: xTRß transcript (accession number: M35356 and M35357) sense 5'-CAAGCACCAAGAACGAAAACC-3' (nucleotide numbers 1535) and antisense 5'-TTGGAAGGTCTGCTCATTCTTCTA-3' (3916), and X. laevis GAPDH transcript (accession number: V41753) sense 5'-CTCATGACAACAGTCCATGCTTTC-3' (558581) and antisense 5'-CTCTGCCATCTCTCCACAGCTT-3' (639618).
Luciferease assay. Sense and antisense oligonucleotides containing the thyroid hormone response elements (TREs), TH/bZIP TRE1 + TRE2 (99 to 63) (Furlow and Brown, 1999), were annealed and introduced into the unique BglII/SacI site in the pGL2 promoter vector (Promega, Madison, WI) making the reporter plasmid pGL2-TRE. xTRß cDNA (kindly provided by Dr. D. D. Brown) was cloned into the EcoRI site of pcDNA3 (Invitrogen, Carlsbad, CA) making the xTRß expression plasmid pcDNA3-xTRß. Plasmids for transfection were purified using QIAGEN (Chatsworth, CA) miniprep kits. For transient transfection assays, X. laevis XL58 cells (0.6 x 105 cells) were seeded in 24-well culture plates (Nunc, Roskilde, Denmark) and cultured in 70% Leibovitz's L-15 medium (Sigma) containing 10% resin-stripped fetal bovine serum (Samuels et al., 1979
) for 15 h at 25°C with air. The next day, the cells were transfected with 500 ng pGL2-TRE, 50 ng pcDNA3-xTRß, and 20 ng pRL-CMV vector (Promega) with 4 µl of the lipofection reagent DOSPER (Roche, Mannheim, Germany). After 6 h, the cells were replenished with 70% Leibovitz's L-15 medium containing 10% resin-stripped fetal bovine serum and further cultured with 2 nM T3, without T3, or with 2 nM T3 and each test chemical at defined concentrations for 24 h at 25°C. The culture media were not changed during this treatment. The cells from each well were harvested and assayed for firefly Photinus pyralis and sea pansy Renilla reniformis luciferase activities, derived from pGL2-TER and pRL-CMV, respectively, by using Dual-Luciferase Reporter Assay System (Promega) according to the manufacturer's directions. Transfection efficiency was normalized using a constant amount of the sea pansy luciferase activity.
Statistical analysis. The data are presented as mean ± SEM. Differences between groups were analyzed with either Student's t-test or Cochran-Cox test to evaluate the significance of the differences; p < 0.05 was considered statistically significant.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
|
|
To confirm whether the EDCs' effects on T3-induced X. laevis metamorphosis were due to their interference with the T3-signaling pathway, we examined the amount of TRß transcript in whole tadpoles. The trß gene is a well-known, early primary T3-response gene in metamorphosing X. laevis tadpoles (Wang and Brown 1993). In X. laevis tadpoles treated with T3 (2 nM), the amount of TRß transcript increased 3035 times on the fifth day after treatment (Figs. 4A and 4B). The amount of TRß transcript on the seventh day after treatment was the same as that on the fifth day (data not shown). Cotreatment of T3 with 3,3',5-trichlorobisphenol A (2 µM), 2,4,6-triiodophenol(1.2 µM), o-t-butylphenol (6 µM) or 2-isopropylphenol (10 µM) significantly inhibited the T3-induced increase in the amount of TRß transcript at the fifth or seventh day of treatment. The inhibition percentages obtained from independent repeated experiments were 39 ± 5% 3,3',5-trichlorobisphenol A (n = 5), 44 ± 7% 2,4,6-triiodophenol (n = 3), 30 ± 8% o-t-butylphenol (n = 4), and 46 ± 10% 2-isopropylphenol (n = 5). These results indicated that the four chemicals tested interfered with the T3-signaling pathway, causing the inhibition of T3-induced metamorphosis.
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
The rank order of binding affinities in the in vitro TTR and TR assays gave similar results, although the TTR assay was more sensitive to the chemicals tested than the TR assay. Both xTTR and xTR had higher affinities for the chlorinated derivatives of bisphenol A and of nonylphenol than for their parent molecules. The relative potency of the chlorinated derivatives was generally dependent upon the degree of chlorination. xTTR and xTR have a binding preference for the two groups of chemicals. The first group contains chlorinated phenolic compounds that have two phenolic rings with chlorines in either ortho position or in both ortho positions with respect to the hydroxy group, such as 3,3',5-trichlorobisphenol A and 3,3',5,5'-tetrachlorobisphenol A. The second group contains chlorinated or brominated phenols that have a single phenol ring with halogens in both ortho positions with respect to the hydroxy group, such as 2,6-dichloro-4-nonylphenol and 2,4,6-triiodophenol. The competitive binding characteristics of these chemicals were similar to previous studies, which analyzed the interactions of the same chlorinated phenolic and phenol compounds with TTRs and TRs from different species (Yamauchi et al., 2003) and different halogenated phenolic and phenol compounds with human TTR (Meerts et al., 2000
; van den Berg, 1990
) and rat TR (Kitamura et al., 2002
).
The binding preference of xTTR and xTR for the chlorinated phenolic compounds, belonging to the first group, may reflect their TH binding properties and the chemical's structural resemblance to THs. Mammalian TTRs have 48 times higher affinity for T4 than for T3 (Chang et al., 1999; Robbins, 1996
) while xTTR has 102 times higher affinity for T3 than for T4 (Yamauchi et al., 2002
). Interestingly, hTTR has 18 times higher affinity for 3,3',5,5'-tetrabromobisphenol A than for 3,3',5-tribromobisphenol A (Meerts et al., 2000
), although xTTR has 2.5 times higher affinity for 3,3',5-trichlorobisphenol A than for 3,3',5,5'-tetrabromobisphenol A. Therefore, it may be concluded that TRs from lower and higher vertebrates and TTRs from lower vertebrates preferentially bind the phenolic compounds with a T3-like structure, while TTRs from higher vertebrates preferentially bind the phenolic compounds with a T4-like structure. This raises the possibility that some EDCs differently affect TTR-mediated plasma TH homeostasis in tadpoles and mammals.
The binding mode of pentabromophenol and tribromophenol provides an example of how the halogenated phenols, belonging to the second group, bind to xTTR. Pentabromophenol and tribromophenol bind to human TTR exclusively in the "reversed mode" with their hydroxyl group oriented toward the mouth of the binding pocket, while T4, which structurally resembles the chemicals belonging to the first group, binds in the "normal mode" with its hydroxyl group oriented toward the center of the binding pocket (Ghosh et al., 2000). Therefore, it is likely that compounds belonging to the first group with a double-ring structure and compounds belonging to the second group with a single-ring structure bind to xTTR in the normal and reverse mode, respectively. These structureactivity relationships may provide clues for deducing the thyroid-disrupting activity of other phenolic and phenol compounds.
Our in vitro and in vivo studies strongly suggest that halogenated phenolic and phenol compounds, such as 3,3'5-trichlorobisphenol A and 2,4,6-triiodophenol at micromolar concentrations, can directly affect T3 binding to xTTR and xTR and exert their T3 antagonist activity in vivo (Table 1), and that o-t-butylphenol and 2-isopropylphenol cause the inhibition of T3-dependent pathways by a molecular mechanism distinct from that for the above halogenated compounds. This is because o-t-butylphenol and 2-isopropylphenol did not compete with 125I-T3 binding to xTR even at 31 µM, but exhibited TH antagonist activity at 610 µM in the metamorphosis assay (Table 1). Therefore, further investigation into which cellular process other than the competitive interaction with T3 binding to xTR is targeted by o-t-butylphenol and 2-isopropylphenol will be necessary.
|
Recently, it was reported that bisphenol A interfered with the thyroid system by recruiting the nuclear corepressor N-CoR to human TR (Moriyama et al., 2002), and that hydroxylated polychlorinated biphenyls (OH-PCBs) caused the partial dissociation of TR/retinoidxreceptor heterodimer complex from TRE (Miyazaki et al., 2004
). The effective concentrations, 0.11.0 µM for bisphenol A and 0.1 pM for OH-PCBs, were 28 orders of magnitude lower than the IC50 values of human TR, 200 µM for bisphenol A (Moriyama et al., 2002
) and 10100 µM for OH-PCBs (Cheek et al., 1999b
), indicating that these compounds affect TR activation without displacing T3, which is in agreement with a recent report (Gauger et al., 2004
). This situation was similar to the results for o-t-butylphenol and 2-isopropylphenol obtained in our studies. Furthermore, chlorinated derivatives of bisphenol A have a molecular structure that resembles those of bisphenol A and OH-PCBs. Therefore, it is possible that phenolic and phenol compounds exert T3 antagonist activity by a mechanism similar to that of bisphenol A or hydroxylated PCBs. Other molecular mechanisms by which the environmental chemicals interfere with the intracellular thyroid signaling pathway have been proposed and include TH metabolizing enzymes (Brouwer et al., 1998
; Cheek et al., 1999a
; Crump et al., 2002
), a crosstalk between TH and other hormonal pathways (Crump et al., 2002
), and other nuclear regulatory proteins (Crump et al., 2002
). Further studies will be necessary to address the precise molecular mechanisms by which phenols and phenolic compounds affect the thyroid signaling pathway.
Bisphenol A is an essential component of epoxy resin. Nonylphenol is an industrial additive used in a wide variety of detergents and plastics. Simple phenols, such as butylphenols and isopropylphenols, have been used in the manufacture of surface-active agents, plasticizers, and phenolic resins, and in many industrial products including oil additives, oil demulsifiers, and antioxidants. A dozen simple phenols are widely distributed in the water environment, such as river water, lake water, groundwater, and seawater (JEA, 1999). Bisphenol A is easily chlorinated by sodium hypochlorite (Fukazawa et al., 2002
), which is used as a bleaching agent in paper recycling plants and as a disinfection agent in sewage treatment plants. In effluents from paper manufacturing plants in Japan, the maximum concentration for the chlorinated derivatives was 7.6 nM and for bisphenol A was 1.6 µM (Fukazawa et al., 2001
). The concentration of 2,4,6-triiodophenol in the environment has been unknown, although iodinated phenols can be easily generated from phenol in iodide water in the presence of chlorine under the experimental conditions (Patnaik and Khoury, 2003
). Considering the IC50 values of xTTR for bisphenol A and of 3,3',5-trichlorobisphenol A, 2.1 µM and 13 nM, respectively, and the effective concentration of bisphenol A required to recruit the nuclear corepressor N-CoR to human TR as reported by Moriyama et al. (2002)
, 0.11.0 µM, their interference with the X. laevis thyroid system could be possible at the concentrations reported in specific environments, although we cannot elucidate how strong an impact these chemicals have on TTR-mediated TH homeostasis from our study.
![]() |
ACKNOWLEDGMENTS |
---|
This work was supported by Grant-in Aid for Scientific Research on Priority Area (A) (No. 13027236, No. 14042223) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, Grant-in Aid for Scientific Research (B) (No. 13559001, No. 16244120) from Japan Society for the Promotion of Science.
The authors declare they have no competing financial interests.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() ![]() |
---|
Bevan, C. L., Porter, D. M., Pradad, A., Howard, M. J., and Henderson, L. P. (2003). Environmental estrogens alter early development in Xenopus laevis. Environ. Health. Perspect. 111, 488496.[ISI][Medline]
Bradford, M. M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248254.[CrossRef][ISI][Medline]
Brouwer, A., Morse, D. C., Lans, M. C., Schuur, A. G., Murk, A. J., Klasson-Wehler, E., et al. (1998). Interactions of persistent environmental organohalogens with the thyroid hormone system: mechanisms and possible consequences for animal and human health. Toxicol. Ind. Health 14, 5984.[ISI][Medline]
Brucker-Davis, F. (1998). Effects of environmental synthetic chemicals on thyroid function. Thyroid 8, 827856.[ISI][Medline]
Byrne, J. J., Carbone, J. P., and Hanson, E. A. (1987). Hypothyroidism and abnormalities in the kinetics of thyroid hormone metabolism in rats treated chronically with polychlorinated biphenyl and polybrominated biphenyl. Endocrinology 121, 520527.[Abstract]
Chang, L., Munro, S. L. A., Richardson, S. J., and Schreiber, G. (1999). Evolution of thyroid hormone binding by transthyretins in birds and mammals. Eur. J. Biochem. 259, 534542.
Cheek, A. O., Ide, C. F., Bollinger, J. E., Rider, C. V., and McLachlan, J. A. (1999a) Alteration of leopard frog (Rana pipiens) metamorphosis by the herbicide acetochlor. Arch. Environ. Contam. Toxicol. 37, 7077.[CrossRef][ISI][Medline]
Cheek, A. O., Kow, K., Chen, J., and McLachlan, J. A. (1999b). Potential mechanisms of thyroid disruption in humans: interaction of organochlorine compounds with thyroid receptor, transthyretin, and thyroid-binding globulin. Environ. Health. Perspect. 107, 273278.[ISI][Medline]
Cheek, A. O., Vonier, P. M., Oberdörster, E., Burow, B. C., and McLachlan, J. A. (1998). Environmental signaling: A biological context for endocrine disruption. Environ. Health. Perspect. 106(Suppl. 1), 510.[ISI][Medline]
Collins, W. T., and Capen, C. C. (1980). Fine structural lesions and hormone alterations in thyroid glands of perinatal rats exposed in utero and by the milk to polychlorinated biphenyls. Am. J. Pathol. 99, 125142.[Abstract]
Collins, W. T., Capen, C. C., Kasza, L., Carter, C., and Dailey, R. E. (1977). Effect of polychlorinated biphenyl (PCB) on the thyroid gland of rats. Ultrastructural and biochemical investigations. Am. J. Pathol. 89, 119130.[ISI][Medline]
Crump, D., Werry, K., Veldhoen, N., Van Aggelen, G., and Helbing. C. C. (2002) Exposure to the herbicide acetochlor alters thyroid hormone-dependent gene expression and metamorphosis in Xenopus laevis. Environ. Health Perspect. 110, 11991205.[ISI][Medline]
Danzo, B. J. (1997). Environmental xenobiotics may disrupt normal endocrine function by interfering with the binding of physiological ligands to steroid receptors and binding proteins. Environ. Health Perspect. 105, 294301.[ISI][Medline]
Dickhoff, W. W., Brown, C. L., Sullivan, C. V., and Bern, H. A. (1990). Fish and amphibian models for developmental endocrinology. J. Exp. Zool. Suppl. 4, 9097.
Dumont, J., Schultz, T. W., Buchanan, M., and Kao, G. (1983). Frog Embryo Teratogenesis Assay-Xenopus (FETAX)- A Short-term Assay Applicable to Complex Environmental Mixtures. In: Short-Term Bioassays in the Analysis of Complex Environmental Mixtures III (M. D.Waters, S. S. Sandhu, J. Lewtas, L. Claxton, N. Chernoff, and S. Nesnow, Eds.), pp. 393405. Plenum, New York.
Fukazawa, H., Hoshino, K., Shiozawa, T., Matsushita, H., and Terao, Y. (2001). Identification and quantification of chlorinated bisphenol A in wastewater from wastepaper recycling plants. Chemoshere 44, 973979.[CrossRef]
Fukazawa, H., Watanabe, M., Shiraishi, F., Shiraishi, H., Shiozawa, T., Matsushita, H., et al. (2002). Formation of chlorinated derivatives of bisphenol A in waste paper recycling plants and their estrogenic activities. J. Health. Sci. 48, 242249.[CrossRef][ISI]
Furlow, J. D., and Brown, D. D. (1999). In vitro and in vivo analysis of the regulation of a transcription factor gene by thyroid hormone during Xenopus laevis metamorphosis. Mol. Endocrinol. 13, 20762089.
Gauger, K. J., Kato, Y., Haraguchi, K., Lehmler, H-J., Robertson, L. W., Bansal, R., et al. (2004). Polychlorinated biphenyls (PCBs) exert thyroid hormone-like effects in the fetal rat brain but do not bind to thyroid hormone receptors. Environ. Health Perspect 112, 516523.[ISI][Medline]
Ghosh, M., Meerts, I. A., Cook, A., Bergman, A., Brouwer, A., and Johnson, L. N. (2000). Structure of human transthyretin complexed with bromophenols: a new mode of binding. Acta Crystallogr. D Biol. Crystallogr. 56, 10851095.[CrossRef][ISI][Medline]
Ishihara, A., Nishiyama, N., Sugiyama, S., and Yamauchi, K. (2003a). The effect of endocrine disrupting chemicals on thyroid hormone binding to Japanese quail transthyretin and thyroid hormone receptor. Gen. Comp. Endocrinol. 134, 3643.[CrossRef][ISI][Medline]
Ishihara, A., Sawatsubashi, S., and Yamauchi, K. (2003b). Endocrine disrupting chemicals: interference of thyroid hormone binding to transthyretins and to thyroid hormone receptors. Mol. Cell. Endocrinol. 199, 105117.[CrossRef][ISI][Medline]
JEA. (1999). Surveillance of endocrine disrupters at public water areas. Tokyo, Japan: Water Quality Management Division, Japan Environment Agency.
Kitamura, S., Jinno, N., Ohta, S., Kuroki, H., and Fujimoto, N. (2002). Thyroid hormone activity of the flame retardants tetrabromobisphenol A and tetrachlorobisphenol A. Biochem. Biophys. Res. Commun. 293, 554559.[CrossRef][ISI][Medline]
Larsson, M., Pettersson, T., and Carlström, A. (1985). Thyroid hormone binding in serum of 15 vertebrate species: Isolation of thyroxine-binding globulin and prealbumin analogs. Gen. Comp. Endocrinol. 58, 360375.[CrossRef][ISI][Medline]
Lennon, A. M. (1992). Purification and characterization of rat brain cytosolic 3,5,3'-triiodo-L-thyronine-binding protein. Evidence for binding activity dependent on NADPH, NADP and thioredoxin. Eur. J. Biochem. 210, 7995.[Abstract]
Lennon, A. M., Osty, J., and Nunez, J. (1980). Cytosol thyroxine-binding protein and brain development. Mol. Cell. Endocrinol. 18, 201214.[CrossRef][ISI][Medline]
Matthews, J., Celius, T., Halgren, R., and Zacharewski, T. (2000). Differential estrogen receptor binding of estrogenic substances: a species comparison. J. Steroid Biochem. Mol. Biol. 74, 223234.[CrossRef][ISI][Medline]
Meerts, I. A., van Zanden, J. J., Luijks, E. A. C., van Leeuwen-Bol, I., Marsh, G., Jakobsson, E., et al. (2000). Potent competitive interactions of some brominated flame retardants and related compounds with human transthyretin in vitro. Toxicol. Sci. 56, 95104.
Miyazaki, W., Iwasaki, T., Takeshita, A., Kuroda, Y., and Koibuchi, N. (2004). Polychlorinated biphenyls suppress thyroid hormone receptor-mediated transcription through a novel mechanism. J. Biol. Chem. 279, 1819518202.
Moccia, R. D., Fox, G. A., and Britton, A. (1986). A quantitative assessment of thyroid histopathology of herring gulls (Larus argentatus) from the Great Lakes and a hypothesis on the causal role of environmental contaminants. J. Wildl. Dis. 22, 6070.[Abstract]
Moriyama, K., Tagami, T., Akamizu, T., Usui, T., Saijo, M., Kanamoto, N., et al. (2002). Thyroid hormone action is disrupted by bisphenol A as an antagonist. J. Clin. Endocrinol. Metab. 87, 51855190.
Nieuwkoop, P. D., and Faber, J. (1975). Normal Table of Xenopus laevis (Duadin), 2nd ed. North-Holland Publishing, Amsterdam.
Patnaik, P., and Khoury, J. (2003) Pathways of phenol-chlorine reactions in iodide waters: diversion from chlorosubstitution to iodosubstitution. Am. Lab. News 35, 2224.
Porterfield, S. P. (1994). Vulnerability of the developing brain to thyroid abnormalities: environmental insult to the thyroid system. Environ. Health Perspect. 102(Suppl. 2), 12530.
Robbins, J. (1996). Thyroid hormone transport proteins and the physiology of hormone binding. In Weiner and Ingbar's The Thyroid, 7th ed. (L. E. Braverman and R. D. Utiger, Eds.), pp. 96110. Lippincott-Raven, Philadelphia.
Rolland, R. M. (2000). A review of chemically-induced alterations in thyroid and vitamin A status from field studies of wildlife and fish. J. Wildl. Dis. 36, 615635.
Samuels, H. H., Stanley, F., and Casanova, J. (1979). Depletion of L-3,5,3'-triiodothyronine and L-thyroxine in euthyroid calf serum for use in cell culture studies of the action of thyroid hormone. Endocrinology 105, 8085.[Abstract]
Sonnenschein, C., and Soto, A. M. (1998). An updated review of environmental estrogen and androgen mimics and antagosists. J. Steroid Biochem. Mol. Biol. 65, 143150.[CrossRef][ISI][Medline]
van den Berg, K. J. (1990). Interaction of chlorinated phenols with thyroxine binding sites of human transthyretin, albumin and thyroid binding globulin. Chem. Biol. Interact. 76, 6375.[CrossRef][ISI][Medline]
Verreault, J., Skaare, J. U., Jenssen, B. M., and Gabrielson, G. W. (2004). Effects of organochlorine contaminants on thyroid hormone levels in arctic breeding glaucous gulls, Larus hyperboreus. Environ. Health Perspect. 112, 532537.[ISI][Medline]
Wang, Z., and Brown, D.D. (1993). Thyroid hormone-induced gene expression program for amphibian tail resorption. J. Biol. Chem. 268, 1627016278.
Yamauchi, K., Eguchi, R., Shimada, N., and Ishihara, A. (2002). The effects of endocrine-disrupting chemicals on thyroid hormone binding to Xenopus laevis transthyretin and thyroid hormone receptor. Clin. Chem. Lab. Med. 40, 12501256.[CrossRef][ISI][Medline]
Yamauchi, K., Ishihara, A., Fukazawa, H., and Terao, Y. (2003). Competitive interactions of chlorinated phenol compounds with 3,3',5-triiodothyronine binding to transthyretin: detection of possible thyroid-disrupting chemicals in environmental waste water. Toxicol. Appl. Pharmacol. 187, 110117.[CrossRef][ISI][Medline]
Yamauchi, K., Kasahara, T., Hayashi, H., and Horiuchi, R. (1993). Purification and characterization of a 3,5,3'-L-triiodothyronine-specific binding protein from bullfrog tadpole plasma: A homolog of mammalian transthyretin. Endocrinology 132, 22542261.[Abstract]
Yamauchi, K., Prapunpoj, P., and Richardson, S. J. (2000). Effect of diethylstilbestrol on thyroid hormone binding to amphibian transthyretins. Gen. Comp. Endocrinol. 119, 329339.[CrossRef][ISI][Medline]
Zoeller, T. R., Dowling, A. L., Herzig, C. T., Iannacone, E. A., Gauger, K. J., and Bansal, R. (2002). Thyroid Hormone, brain development, and the environment. Environ. Health Perspect. 110(Suppl. 3), 355361.