Laccase-Mediated Transformations of Endocrine Disrupting Chemicals Abolish Binding Affinities to Estrogen Receptors and Their Estrogenic Activity in Zebrafish

2012 ◽  
Vol 168 (4) ◽  
pp. 864-876 ◽  
Author(s):  
Cristina Torres-Duarte ◽  
María Teresa Viana ◽  
Rafael Vazquez-Duhalt
Keyword(s):  
Estrogen Receptors ◽  
Estrogenic Activity ◽  
Endocrine Disrupting Chemicals ◽  
Binding Affinities ◽  
Endocrine Disrupting

scholarly journals Predicting Potential Endocrine Disrupting Chemicals Binding to Estrogen Receptor α (ERα) Using a Pipeline Combining Structure-Based and Ligand-Based in Silico Methods

2021 ◽  
Vol 22 (6) ◽  
pp. 2846
Author(s):  
Asma Sellami ◽  
Matthieu Montes ◽  
Nathalie Lagarde
Keyword(s):  
Estrogen Receptors ◽  
Nuclear Receptors ◽  
Environmental Protection Agency ◽  
Glucocorticoid Receptors ◽  
Estrogenic Activity ◽  
Endocrine Disrupting Chemicals ◽  
Peroxisome Proliferator ◽  
Consensus Protocol ◽  
Endocrine Disrupting ◽  
Pharmacophore Models

The estrogen receptors α (ERα) are transcription factors involved in several physiological processes belonging to the nuclear receptors (NRs) protein family. Besides the endogenous ligands, several other chemicals are able to bind to those receptors. Among them are endocrine disrupting chemicals (EDCs) that can trigger toxicological pathways. Many studies have focused on predicting EDCs based on their ability to bind NRs; mainly, estrogen receptors (ER), thyroid hormones receptors (TR), androgen receptors (AR), glucocorticoid receptors (GR), and peroxisome proliferator-activated receptors gamma (PPARγ). In this work, we suggest a pipeline designed for the prediction of ERα binding activity. The flagged compounds can be further explored using experimental techniques to assess their potential to be EDCs. The pipeline is a combination of structure based (docking and pharmacophore models) and ligand based (pharmacophore models) methods. The models have been constructed using the Environmental Protection Agency (EPA) data encompassing a large number of structurally diverse compounds. A validation step was then achieved using two external databases: the NR-DBIND (Nuclear Receptors DataBase Including Negative Data) and the EADB (Estrogenic Activity DataBase). Different combination protocols were explored. Results showed that the combination of models performed better than each model taken individually. The consensus protocol that reached values of 0.81 and 0.54 for sensitivity and specificity, respectively, was the best suited for our toxicological study. Insights and recommendations were drawn to alleviate the screening quality of other projects focusing on ERα binding predictions.

scholarly journals Symbiotic Gene Activation is Interrupted by Endocrine Disrupting Chemicals

2001 ◽  
Vol 1 ◽  
pp. 653-655 ◽  
Author(s):  
Jennifer E. Fox ◽  
Matthew E. Burow ◽  
John A. McLachlan
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptors ◽  
Mammalian Cell Culture ◽  
Endocrine Disrupting Chemicals ◽  
Gene Activation ◽  
Symbiotic Gene ◽  
Endocrine Disrupting ◽  
Plant Chemicals ◽  
By Products

Endocrine disrupting chemicals (EDCs) include organochlorine pesticides, plastics manufacturing by-products, and certain herbicides[1]. These chemicals have been shown to disrupt hormonal signaling in exposed wildlife, lab animals, and mammalian cell culture by binding to estrogen receptors (ER-α and ER-β) and affecting the expression of estrogen responsive genes[2,3]. Additionally, certain plant chemicals, termed phytoestrogens, are also able to bind to estrogen receptors and modulate gene expression, and as such also may be considered EDCs[4]. One example of phytoestrogen action is genistein, a phytochemical produced by soybeans, binding estrogen receptors, and changing expression of estrogen responsive genes which certain studies have linked to a lower incidence of hormonally related cancers in Japanese populations[5]. Why would plants make compounds that are able to act as estrogens in the human body? Obviously, soybeans do not intentionally produce phytoestrogens to prevent breast cancer in Japanese women.

scholarly journals Molecular Basis for Endocrine Disruption by Pesticides Targeting Aromatase and Estrogen Receptor

2020 ◽  
Vol 17 (16) ◽  
pp. 5664 ◽  
Author(s):  
Chao Zhang ◽  
Tiziana Schilirò ◽  
Marta Gea ◽  
Silvia Bianchi ◽  
Angelo Spinello ◽  
...  
Keyword(s):  
Competitive Inhibition ◽  
Estrogenic Activity ◽  
Endocrine Disrupting Chemicals ◽  
Binding Mode ◽  
Inhibition Mechanism ◽  
Aromatase Activity ◽  
Docking Simulations ◽  
Potential Binding ◽  
Endocrine Disrupting ◽  
17Β Estradiol

The intensive use of pesticides has led to their increasing presence in water, soil, and agricultural products. Mounting evidence indicates that some pesticides may be endocrine disrupting chemicals (EDCs), being therefore harmful for the human health and the environment. In this study, three pesticides, glyphosate, thiacloprid, and imidacloprid, were tested for their ability to interfere with estrogen biosynthesis and/or signaling, to evaluate their potential action as EDCs. Among the tested compounds, only glyphosate inhibited aromatase activity (up to 30%) via a non-competitive inhibition or a mixed inhibition mechanism depending on the concentration applied. Then, the ability of the three pesticides to induce an estrogenic activity was tested in MELN cells. When compared to 17β-estradiol, thiacloprid and imidacloprid induced an estrogenic activity at the highest concentrations tested with a relative potency of 5.4 × 10−10 and 3.7 × 10−9, respectively. Molecular dynamics and docking simulations predicted the potential binding sites and the binding mode of the three pesticides on the structure of the two key targets, providing a rational for their mechanism as EDCs. The results demonstrate that the three pesticides are potential EDCs as glyphosate acts as an aromatase inhibitor, whereas imidacloprid and thiacloprid can interfere with estrogen induced signaling.

scholarly journals In Vivo Testing System for Determining the Estrogenic Activity of Endocrine-Disrupting Chemicals(EDCs) in Goldfish (Carassius auratus).

2001 ◽  
Vol 47 (2) ◽  
pp. 213-218 ◽  
Author(s):  
Hiroshi Ishibashi ◽  
Katsuyasu Tachibana ◽  
Mutsuyosi Tsuchimoto ◽  
Kiyoshi Soyano ◽  
Yasuhiro Ishibashi ◽  
...  
Keyword(s):  
Carassius Auratus ◽  
Estrogenic Activity ◽  
Endocrine Disrupting Chemicals ◽  
Testing System ◽  
Goldfish Carassius Auratus ◽  
Endocrine Disrupting ◽  
In Vivo Testing

scholarly journals Hormone-Activated Estrogen Receptors in Annelid Invertebrates: Implications for Evolution and Endocrine Disruption

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1731-1738 ◽  
Author(s):  
June Keay ◽  
Joseph W. Thornton
Keyword(s):  
Estrogen Receptors ◽  
Endocrine Disruption ◽  
Endocrine Disrupting Chemicals ◽  
Estrogen Signaling ◽  
Estrogen Sensitivity ◽  
Endocrine Disrupting ◽  
Platynereis Dumerilii ◽  
Bilaterian Animal ◽  
Capitella Capitata ◽  
And Behavior

As the primary mediators of estrogen signaling in vertebrates, estrogen receptors (ERs) play crucial roles in reproduction, development, and behavior. They are also the major mediators of endocrine disruption by xenobiotic pollutants that mimic or block estrogen action. ERs that are sensitive to estrogen and endocrine disrupters have long been thought to be restricted to vertebrates: although there is evidence for estrogen signaling in invertebrates, the only ERs studied to date, from mollusks and cephalochordates, have been insensitive to estrogen and therefore incapable of mediating estrogen signaling or disruption. To determine whether estrogen sensitivity is ancestral or a unique characteristic of vertebrate ERs, we isolated and characterized ERs from two annelids, Platynereis dumerilii and Capitella capitata, because annelids are the sister phylum to mollusks and have been shown to produce and respond to estrogens. Functional assays show that annelid ERs specifically activate transcription in response to low estrogen concentrations and bind estrogen with high affinity. Furthermore, numerous known endocrine-disrupting chemicals activate or antagonize the annelid ER. This is the first report of a hormone-activated invertebrate ER. Our results indicate that estrogen signaling via the ER is as ancient as the ancestral bilaterian animal and corroborate the estrogen sensitivity of the ancestral steroid receptor. They suggest that the taxonomic scope of endocrine disruption by xenoestrogens may be very broad and reveal how functional diversity evolved in a gene family central to animal endocrinology.

2D/2D Bi2WO6/Protonated g-C3N4 Step-scheme Heterojunctions for Enhancing Photodegradation of 17β-Estradiol: Promotional Role of Electrostatic Interaction

2022 ◽  
Author(s):  
Yashi Qing ◽  
Yanxiang Li ◽  
Dan Hu ◽  
Zhiwei Guo ◽  
Yujie Yang ◽  
...  
Keyword(s):  
Human Health ◽  
Electrostatic Interaction ◽  
Estrogenic Activity ◽  
Endocrine Disrupting Chemicals ◽  
Endocrine Disrupting ◽  
17Β Estradiol

17β-Estradiol (E2) is a type of endocrine disrupting chemicals (EDCs) with the strongest estrogenic activity which poses a huge threat to the ecosystems and human health even at extremely low...

In vivo and in vitro Screening of Endocrine Disrupting Chemicals with Estrogenic activity in Japanese Quail

2005 ◽  
Vol 16 (1) ◽  
pp. 19-27 ◽  
Author(s):  
Kiyoshi Shimada ◽  
Yonju Ha ◽  
Akira Tsukada ◽  
Noboru Saito ◽  
Shinobu Maekawa ◽  
...  
Keyword(s):  
Japanese Quail ◽  
Estrogenic Activity ◽  
Endocrine Disrupting Chemicals ◽  
Endocrine Disrupting
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