Rapid Screening of Environmental Chemicals for Estrogen Receptor Binding Capacity

Bolger, Randall E.; Wiese, Thomas E.; Ervin, Kerry; Nestich, Scott; Checovich, W J

doi:10.2307/3434229

Cited by 84 publications

(127 citation statements)

References 37 publications

(53 reference statements)

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“…E2 and OHT were tested as positive controls to validate the SPR method. The K D value of E2 (0.31 nM) obtained in our assay is in good agreement with the results of fluorescence polarization (0.6 nM), 33 radio-labeled competitive assay (0.26 nM, 0.13 nM) 34,35 and SPR based assay (0.9 nM). 30 The K D value of OHT (5.7 nM) is also within the range of 0.2−18 nM obtained by other reported methods.…”

Section: ■ Results and Discussionsupporting

confidence: 89%

Assessment of Estrogenic Activity of Perfluoroalkyl Acids Based on Ligand-induced Conformation State of Human Estrogen Receptor

Gao

Guo

2012

Environ. Sci. Technol.

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Perfluoroalkyl acids (PFAAs) have been reported to interfere with the endocrine system in vivo by mimicking endogenous hormone activities and causing adverse effects. Some exoestrogens bind to estrogen receptor (ER) and subsequently induce an ERmediated response. The transcriptional activity of ER is regulated by its distinct conformational states that are the results of ligand binding. In this work, a biosensor based on surface plasmon resonance (SPR) technique was developed which can discriminate between agonist and antagonist of human ERα (hERα) by monitoring the conformation state of the protein induced by ligand binding. The biosensor utilized the specific interaction between hERα and conformation-selective peptides. Six PFAAs with different chain lengths and acid groups were tested by the biosensor, and perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were found to be ER agonists. Kinetic analyses of direct interaction between PFAAs and hERα by SPR revealed that PFOS and PFOA were both weak binders of ER with K D values of 2.19 and 107 μM respectively, whereas the other four PFAAs did not bind with ER. To understand the differences in ER binding affinity and estrogenic activity among the six PFAAs, molecular docking based on the crystal structure of hERα ligand binding domain was performed. PFOS and PFOA were efficiently docked with hERα and formed hydrogen bonds with Arg394 in a manner similar to estradiol. Overall, the two 8-carbon PFAAs were assessed as weak agonists of hERα and are of potential concern.

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Section: ■ Results and Discussionsupporting

confidence: 89%

Assessment of Estrogenic Activity of Perfluoroalkyl Acids Based on Ligand-induced Conformation State of Human Estrogen Receptor

Gao

Guo

2012

Environ. Sci. Technol.

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“…Both the EC 50 values in the receptor binding assay of bisphenol A and 4,4-OHBP (Bolger et al 1998;Kuiper et al 1998) and the growth stimulation of 4-OHBP, 4,4-OHBP and bisphenol A were in the same range as reported by others (Soto et al 1995). In accordance with the relatively low binding affinity to the oestrogen receptors, all the chemicals tested expressed a much lower proliferative potential than 17b-oestradiol (table 1).…”

Section: Discussionsupporting

confidence: 75%

Effects of the Environmental Oestrogens Bisphenol A, Tetrachlorobisphenol A, Tetrabromobisphenol A, 4‐Hydroxybiphenyl and 4,4′‐Dihydroxybiphenyl on Oestrogen Receptor Binding, Cell Proliferation and Regulation of Oestrogen Sensitive Proteins in the Human Breast Cancer Cell Line MCF‐7

Olsen¹,

Meussen‐Elholm²,

Samuelsen³

et al. 2003

Pharmacology & Toxicology

108

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Bisphenol A is extensively used in the manufacturing of epoxy resins and polycarbonate plastics, whereas several brominated and chlorinated analogues are used as flame retardants and intermediates in the plastic industry. Due to the structural relationship between these chemicals and the high production volumes, we wanted to characterize and compare their potential oestrogen-like potency using several end-points in MCF-7 cells: induction of pS2 protein and progesterone receptor, reduction of oestrogen receptor level, and stimulation of cell growth. Bisphenol A, tetrachloro-and tetrabromobisphenol A, 4-hydroxybiphenyl and 4,4ø-dihydroxybiphenyl all showed oestrogen-like properties in MCF-7 cells. The chemicals tested had affinity to the oestrogen receptor isolated from MCF-7 cells, although their EC 50 s were 1,000 to 80,000 times higher than the EC 50 of 17b-oestradiol. Bisphenol A and 4-hydroxybiphenyl induced cell growth in MCF-7 cells, and the highest test concentrations induced responses, apparently exceeding the cell growth induced by 17b-oestradiol. The other chemicals tested induced less than 50% of the maximum 17b-oestradiol-stimulated cell growth. Bisphenol A, 4-hydroxybiphenyl, tetrabromobisphenol A and tetrachlorobisphenol A all increased the level of the oestrogen-regulated proteins, progesterone receptor and pS2, whereas 4,4ø-dihydroxybiphenyl showed no such effect. Bisphenol A was the only chemical tested that clearly mimicked 17b-oestradiol in its ability to reduce the level of cytosolic oestrogen receptors in MCF-7 cells. By measuring several oestrogen-dependent endpoints it seems that some xeno-oestrogens cause an imbalanced oestrogen-response. Their ability and potency in mimicking 17b-oestrogen in one parameter is not necessarily accompanied by a similar effect in another oestrogen-linked parameter.

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“…The introduction of fluorescent probes, has made possible the measurement of relative binding affinities using fluorescence polarization by the utilization of fluorescein-labeled E2 (Bolger et al, 1998). The radio-labeled version of the ligand-ER binding assay has the advantage to allow the measurements of the binding activity of purified compounds on both crude protein extracts and intact living cells expressing ERs.…”

Section: ( ( ( ( (A) Ligand-er Binding Assays A) Ligand-er Binding Asmentioning

confidence: 99%

Tools to evaluate estrogenic potency of dietary phytoestrogens:A consensus paper from the EU Thematic Network “Phytohealth” (QLKI-2002-2453)

Saarinen

Bingham²,

Lorenzetti

et al. 2006

Genes Nutr

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Rapid Screening of Environmental Chemicals for Estrogen Receptor Binding Capacity

Abstract: Over the last few years, an increased awarenes of endocrine disrupting chemicals (EDCs)

Cited by 84 publications

References 37 publications

Assessment of Estrogenic Activity of Perfluoroalkyl Acids Based on Ligand-induced Conformation State of Human Estrogen Receptor

Assessment of Estrogenic Activity of Perfluoroalkyl Acids Based on Ligand-induced Conformation State of Human Estrogen Receptor

Effects of the Environmental Oestrogens Bisphenol A, Tetrachlorobisphenol A, Tetrabromobisphenol A, 4‐Hydroxybiphenyl and 4,4′‐Dihydroxybiphenyl on Oestrogen Receptor Binding, Cell Proliferation and Regulation of Oestrogen Sensitive Proteins in the Human Breast Cancer Cell Line MCF‐7

Tools to evaluate estrogenic potency of dietary phytoestrogens:A consensus paper from the EU Thematic Network “Phytohealth” (QLKI-2002-2453)

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