Effects of bisphenol A on thyroid hormone-dependent up-regulation of thyroid hormone receptor alpha and beta and down-regulation of retinoid X receptor gamma in Xenopus tail culture.
ABSTRACT We investigated effects of different concentrations (10(-7) - 10(-5) M) of bisphenol A (BPA), which is known as an estrogenic and anti-thyroid hormonal endocrine disrupter, on the expression of thyroid hormone receptor (TR) alpha and beta and retinoid X receptor (RXR) gamma mRNA in tails of stage 52-54 Xenopus tadpoles in organ culture in the presence or absence of different concentrations of triiodo-thyronine (T(3)). In the absence of T(3), BPA at any concentration examined did not show remarkable effects on tail length but blocked 10(-7) M T(3)-induced tail resorption in a concentration-dependent manner. Semi-quantitative analyses of TRalpha and TRbeta mRNAs by RT-PCR in the tail specimens indicated that BPA shows an apparent antagonistic effect towards the receptors and reduced their mRNA levels relative to controls. When administered together with 10(-7) M T(3), the antagonistic effects of BPA were detected more clearly and dose-dependently. While BPA prevented the autoinduction of both TRalpha and TRbeta genes by T(3), the effect was less marked on TRalpha than on TRbeta. BPA also moderately suppressed RXRgamma gene expression. Gene expression of RXRgamma, a partner for heterodimer formation of TRs, was supressed by T(3) alone and also by BPA alone, but no additive effects were observed so far as studied. The present study indicates that a relatively low concentration of BPA, 10(-7) M, as compared with those examined previously (10(-5) to 10(-4) M) by us and other investigators, acts as an antagonist of T(3) through suppression of TRalpha and TRbeta gene expression in Xenopus tail in culture.
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ABSTRACT: Classically, thyroid hormones (THs) have been primarily associated with postembryonic development (Tata, 1968), notably metamorphosis in anuran amphibians and flat fish. This period is parallel to the perinatal period in man and many marked developmental transitions in other species. As amply described in other chapters, metamorphosis is characterized by a peak of thyroxine (T(4)) and triiodothyronine (T(3)) that is synchronous with the metamorphic climax. In contrast, the developmental period that characterizes embryonic development prior to the significant production of TH by the endogenous thyroid gland has received little attention. Furthermore, the prevailing concepts of TH physiology during this period have been framed by two observations in amphibians and mammals: first, TRs are expressed, while circulating TH levels are much lower than those during metamorphosis and, second, extrapolating from the knowledge largely obtained from in vitro models, in the absence of TH, the aporeceptor represses target gene transcription during premetamorphic development. We propose to revisit both concepts in the light of accumulating data, first, on TH availability both in eggs and in embryos and, second, on the increasing knowledge of the complexity of TR and TH control of transcription.Current Topics in Developmental Biology 01/2013; 103:365-96. DOI:10.1016/B978-0-12-385979-2.00013-7 · 4.21 Impact Factor
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ABSTRACT: Synthetic endocrine-disrupting chemicals (EDCs) have been found in surface waters throughout the United States, and are known to enter waterways via discharge from wastewater treatment plants (WWTPs). Studies addressing EDCs in wastewater do not examine their specific sources upstream of WWTPs. Presented here are results of a pilot study of potential sources of selected EDCs within an urban wastewater service area. Twenty-one wastewater samples were collected from a range of sites, including 16 residential, commercial, or industrial samples, and five samples from influent and effluent streams at the WWTP. Samples were analyzed for the following known and suspected EDCs: five phthalates, bisphenol A (BPA), triclosan, 4-nonylphenol (NP), and tris(2-chloroethyl) phosphate (TCEP), using well-established methods (EPA 625 and USGS O-1433-01). Twenty of 21 samples contained at least one EDC. Phthalates were widely detected; one or more phthalate compound was identified in 19 of 21 samples. Measurement of two phthalates in a field blank sample suggests that the accuracy of sample detections for these two compounds may be compromised by background contamination. Triclosan was detected in nine samples, BPA in five samples, and TCEP in four samples; NP was not detected. The results of this and future source-specific studies may be used to develop targeted pollution prevention strategies to reduce levels of EDCs in wastewater.Science of The Total Environment 09/2008; 405(1-3):153-60. DOI:10.1016/j.scitotenv.2008.06.033 · 4.10 Impact Factor
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ABSTRACT: Bisphenol A (BPA) is an endocrine disruptor that can mimic the action of estrogens by interacting with hormone receptors and is, therefore, potentially able to influence reproductive functions in vertebrates. Although information about the interaction with the endocrine systems in invertebrates is limited, it has also been shown its effect on reproductive and developmental parameters in these organisms. As little is known about its mechanism of action in aquatic invertebrates, we have examined the effects of BPA on the expression of some selected genes, including housekeeping, stress-induced and hormone-related genes in Chironomus riparius larvae, a widely used organism in aquatic ecotoxicology. The levels of different gene transcripts were measured by Northern blot or by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Exposure to BPA (3 mgl(-1), 12-24h) did not affect the levels of rRNA or those of mRNAs for both L11 or L13 ribosomal proteins, selected as examples of housekeeping genes involved in ribosome biogenesis. Nevertheless, BPA treatment induced the expression of the HSP70 gene. Interestingly, it was found that BPA significantly increases the mRNA level of the ecdysone receptor (EcR). These results show for the first time that exposure to endocrine disrupting chemicals, such as BPA, can selectively affect the expression of the ecdysone receptor gene suggesting a direct interaction with the insect endocrine system. Furthermore, this finding suggests a common way of BPA action, shared by vertebrates and invertebrates, through interaction with steroid hormone receptors. Our study adds a new element, the EcR, which may be a useful tool for the screening of environmental xenoestrogens in insects.Chemosphere 06/2008; 71(10):1870-6. DOI:10.1016/j.chemosphere.2008.01.033 · 3.50 Impact Factor