Document Detail

Endocrine disrupting chemicals targeting estrogen receptor signaling: identification and mechanisms of action.
MedLine Citation:
PMID:  21053929     Owner:  NLM     Status:  MEDLINE    
Many endocrine disrupting chemicals (EDCs) adversely impact estrogen signaling by interacting with two estrogen receptors (ERs): ERα and ERβ. Though the receptors have similar ligand binding and DNA binding domains, ERα and ERβ have some unique properties in terms of ligand selectivity and target gene regulation. EDCs that target ER signaling can modify genomic and nongenomic ER activity through direct interactions with ERs, indirectly through transcription factors such as the aryl hydrocarbon receptor (AhR), or through modulation of metabolic enzymes that are critical for normal estrogen synthesis and metabolism. Many EDCs act through multiple mechanisms as exemplified by chemicals that bind both AhR and ER, such as 3-methylcholanthrene. Other EDCs that target ER signaling include phytoestrogens, bisphenolics, and organochlorine pesticides, and many alter normal ER signaling through multiple mechanisms. EDCs can also display tissue-selective ER agonist and antagonist activities similar to selective estrogen receptor modulators (SERMs) designed for pharmaceutical use. Thus, biological effects of EDCs need to be carefully interpreted because EDCs can act through complex tissue-selective modulation of ERs and other signaling pathways in vivo. Current requirements by the U.S. Environmental Protection Agency require some in vitro and cell-based assays to identify EDCs that target ER signaling through direct and metabolic mechanisms. Additional assays may be useful screens for identifying EDCs that act through alternative mechanisms prior to further in vivo study.
Erin K Shanle; Wei Xu
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2010-11-05
Journal Detail:
Title:  Chemical research in toxicology     Volume:  24     ISSN:  1520-5010     ISO Abbreviation:  Chem. Res. Toxicol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-14     Completed Date:  2011-05-10     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  8807448     Medline TA:  Chem Res Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6-19     Citation Subset:  IM    
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MeSH Terms
Endocrine Disruptors / chemistry*,  toxicity
Hydrocarbons, Chlorinated / chemistry,  toxicity
Phenols / chemistry,  toxicity
Phytoestrogens / chemistry,  toxicity
Protein Structure, Tertiary
Receptors, Estrogen / chemistry,  metabolism*
Signal Transduction
Grant Support
R01 CA125387/CA/NCI NIH HHS; R01 CA125387-05/CA/NCI NIH HHS; R01CA125387/CA/NCI NIH HHS; R03 MH089442/MH/NIMH NIH HHS; R03 MH089442-02/MH/NIMH NIH HHS; R03MH089442/MH/NIMH NIH HHS; T32 ES007015/ES/NIEHS NIH HHS; T32 ES007015-33/ES/NIEHS NIH HHS
Reg. No./Substance:
0/Endocrine Disruptors; 0/Hydrocarbons, Chlorinated; 0/Phenols; 0/Phytoestrogens; 0/Receptors, Estrogen

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