Estrogenic Activities of 517 Chemicals by Yeast Two-Hybrid Assay
01 Aug 2000-Journal of Health Science (The Pharmaceutical Society of Japan)-Vol. 46, Iss: 4, pp 282-298
TL;DR: A simple and rapid screening method using the yeast two-hybrid system based on the ligand-dependent interaction of nuclear hormone receptors with coactivators to test the estrogenic activity of chemicals.
Abstract: One of the urgent tasks in understanding endocrine disruptors (EDs) is to compile a list of suspected substances among the huge number of chemicals by using the screening test method. We developed a simple and rapid screening method using the yeast two-hybrid system based on the ligand-dependent interaction of nuclear hormone receptors with coactivators. To date, we have tested the estrogenic activity of more than 500 chemicals including natural substances, medicines, pesticides, and industrial chemicals. 64 compounds were evaluated as positive, and most of these demonstrated a common structure; phenol with a hydrophobic moiety at the para-position without bulky groups at the ortho-position. These results are expected to facilitate further risk assessment of chemicals.
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TL;DR: It is confirmed that chlorination is effective at removing BPA in drinking water and the estrogenic activity of water samples, evaluated by ER-CALUX assay, was found to significantly decrease after 10min of chlorination, indicating that the generated compounds have significantly lower estrogenicActivity.
32 citations
TL;DR: Goldfish are useful for the investigation of EDCs under various conditions since they are relatively small in size, and the ELISA established in the present study will contribute to various types of research.
Abstract: Vitellogenin (VTG) is believed to be an effective and sensitive biomarker to detect the effects of endocrine-disrupting chemicals (EDCs) on fish. An enzymelinked immunosorbent assay (ELISA) was developed in this study for the quantification of VTG in goldfish (Carassius auratus) blood plasma using a monoclonal antibody against carp lipovitellin which is known to cross-react with goldfish VTG, and a working range of 7.8 to 500 ng VTG/ml was established. A laboratory study involving the dosing of male goldfish for 28 days with a range of bisphenol-A (BPA) concentrations was conducted, and the established ELISA was used. There was no significant induction of VTG at the concentrations of 1 and 10 μg/l. Exposure to 100 μg/l and 1000 μg/l BPA for 28 days significantly elevated plasma VTG concentrations to 201 ± 90 μg/ml and 104552 ± 24920 μg/ml, respectively. To confirm the effect of temperature on VTG induction, male goldfish were exposed to the nominal concentration of 17β-es-tradiol (E2) 100 μg/l at 10° and 30°C for 10 days. Plasma VTG concentration in male goldfish increased more quickly in the fish exposed at 30°C than in those at 10°C. In addition, the plasma VTG concentration in the 30°C group (10463 ± 3268 μg/ml) was higher than that of the 10°C group (1.42 ± 1.6 μg/ml) after 1 day of exposure. Thus goldfish are useful for the investigation of EDCs under various conditions since they are relatively small in size, and the ELISA established in the present study will contribute to various types of research.
32 citations
TL;DR: The rats prenatally exposed to DBP had seminiferous tubule degeneration and atypical hyperplasia of LCs during adulthood, which was associated with an increase in expression of ERα and a decrease of ERβ and AR in the testis.
Abstract: Estrogens and androgens affect male and female reproductive systems. Recently, we reported that prenatal di(n-butyl) phthalate (DBP) exposure induced atypical Leydig cells (LCs) hyperplasia during adulthood. The present study investigated the expression of estrogen receptor α (ERα), estrogen receptor β (ERβ), and androgen receptor (AR) in LCs of 5-, 7-, 9-, 14-, and 17-week-old Sprague-Dawley (srl) rats whose dams had been administered DBP intragastrically at 100 mg/kg/day or the vehicle (corn oil) from days 12 to 21 postconception. Immunohistochemical, Western blotting, and reverse transcription polymerase chain reaction analyses revealed that the expressions of ERα, ERβ, and AR proteins and mRNAs in the DBP group were similar to those of the vehicle group at 5 and 7 weeks, but significantly higher ERα and lower ERβ and AR levels were observed in the DBP group at 9 to 17 weeks. The rats prenatally exposed to DBP had seminiferous tubule degeneration and atypical hyperplasia of LCs during adulthood, which was associated with an increase in expression of ERα and a decrease of ERβ and AR in the testis.
32 citations
Cites background from "Estrogenic Activities of 517 Chemic..."
...However, DBP was found to be capable of binding to estrogen receptor a (ERa) and enhancing the proliferation of an MCF-7 cell line expressing ERa (Nishihara et al. 2000; Jobling et al. 1995; Harris et al. 1997; Zacharewski et al. 1998)....
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...However, DBP was found to be capable of binding to estrogen receptor a (ERa) and enhancing the proliferation of an MCF-7 cell line expressing ERa (Nishihara et al. 2000; Jobling et al. 1995; Harris et al. 1997; Zacharewski et al. 1998)....
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TL;DR: The chemical structures of six isoflavones (1-6 ) isolated from the kudzu root ( Pueraria lobata ) were elucidated on the basis of the NMR and MS analyses to be four Isoflavone C -glycosides as 6″- O -α- d -glucopyranosylpuerarin (1), puerarin(2), 3′-methoxypuerin (3), 6″ O - α-d -apiofranosylperarin (4), and two ag
32 citations
TL;DR: The interest in performing a screening battery and in adopting an integrative approach for identifying the potential of different compounds from a chemical family to interfere with the endocrine system is confirmed.
32 citations
References
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Book•
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01 Jan 1996
TL;DR: The cause of disruptions in animal breeding cycles, accompanied by increases in birth defects, sexual abnormalities and reproductive failure, is traced to the pervasive presence in the environment of chemicals that mimic hormones and trick the reproductive system.
Abstract: For years, scientists have noticed disruptions in animal breeding cycles, accompanied by increases in birth defects, sexual abnormalities and reproductive failure. Humans are not immune either, with sperm counts dropping by as much as 50% in recent decades and with women seeing a rise in hormone-related cancers, endometriosis and other disorders. This book traces the cause of these aberrations and diseases to the pervasive presence in the environment of chemicals that mimic hormones and trick the reproductive system. The conclusions are as obvious as they are inescapable - unless we make vital changes in the way we manufacture and employ the artefacts of our "good life", there will be no life at all.
917 citations