Impact of Induced Fit on Ligand Binding to the Androgen Receptor:  A Multidimensional QSAR Study To Predict Endocrine-Disrupting Effects of Environmental Chemicals

2005 ◽  
Vol 48 (18) ◽  
pp. 5666-5674 ◽  
Author(s):  
Markus A. Lill ◽  
Fabienne Winiger ◽  
Angelo Vedani ◽  
Beat Ernst
Keyword(s):  
Androgen Receptor ◽  
Ligand Binding ◽  
Environmental Chemicals ◽  
Induced Fit ◽  
Qsar Study ◽  
Endocrine Disrupting

scholarly journals SAT-718 Inhibition of Androgen Receptor Activity by DDE Is Affected by Mutations in the BF3 Site

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Andrea Lozano ◽  
Evangelia Kotsikorou ◽  
Frank B Dean
Keyword(s):  
Androgen Receptor ◽  
Ligand Binding ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Hek293 Cells ◽  
Luciferase Assay ◽  
Breakdown Product ◽  
Reporter System ◽  
Surface Binding ◽  
Endocrine Disrupting

Abstract The androgen receptor (AR) plays an important role in the development of the male phenotype and traits. Some diphenyl compounds inhibit AR activity by binding to a hydrophobic surface binding site, BF3. A similar diphenyl structure is found in 4,4’ DDT and its breakdown product 4,4’ DDE. Previous results showed that DDT and DDE induced the release of bound dihydrotestosterone from the AR ligand binding domain, with IC50 values ranging from 54 to 82uM. This suggested that DDT and related compounds may act as endocrine disrupting chemicals by binding to the BF3 site and inducing allosteric changes in the AR structure, disrupting binding of the steroid to the ligand binding domain. Here, an AR reporter system was transiently transfected into HEK293 cells and AR activity was measured using a dual luciferase assay. The system was used to measure the response of the AR protein to varying concentrations of dihydrotestosterone in the presence and absence of DDE. DDE inhibited the activation of AR by dihydrotestosterone under these conditions. Five mutant AR genes with amino acid changes in the BF3 site were tested for alterations in the ability of DDE to disrupt AR activity. The five mutations tested were F673K, F673W, G724R, G724M, and L830D. The ability of DDE to inhibit AR activity was reduced by the mutations in the BF3 site. These results suggest that DDE acts as an endocrine disrupting chemical (EDC) by binding to the BF3 site and allosterically regulating AR activity.

QSAR study of natural, synthetic and environmental endocrine disrupting compounds for binding to the androgen receptor

2005 ◽  
Vol 16 (4) ◽  
pp. 349-367 ◽  
Author(s):  
C. Y. Zhao ◽  
R. S. Zhang ◽  
H. X. Zhang ◽  
C. X. Xue ◽  
H. X. Liu ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Endocrine Disrupting Compounds ◽  
Qsar Study ◽  
Endocrine Disrupting

Environmental exposures to endocrine disrupting chemicals (EDCs) and their role in endometriosis: a systematic literature review

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Diksha Sirohi ◽  
Ruqaiya Al Ramadhani ◽  
Luke D. Knibbs
Keyword(s):  
Bisphenol A ◽  
Phthalate Esters ◽  
Endocrine Disrupting Chemicals ◽  
Environmental Pollutants ◽  
Positive Association ◽  
Environmental Chemicals ◽  
Reproductive Age ◽  
Organochlorinated Pesticides ◽  
Endocrine Disrupting ◽  
The Relationship

AbstractPurposeEndocrine-related diseases and disorders are on the rise globally. Synthetically produced environmental chemicals (endocrine-disrupting chemicals (EDCs)) mimic hormones like oestrogen and alter signalling pathways. Endometriosis is an oestrogen-dependent condition, affecting 10–15% of women of the reproductive age, and has substantial impacts on the quality of life. The aetiology of endometriosis is believed to be multifactorial, ranging from genetic causes to immunologic dysfunction due to environmental exposure to EDCs. Hence, we undertook a systematic review and investigated the epidemiological evidence for an association between EDCs and the development of endometriosis. We also aimed to assess studies on the relationship between body concentration of EDCs and the severity of endometriosis.MethodFollowing PRISMA guidelines, a structured search of PubMed, Embase and Scopus was conducted (to July 2018). The included studies analysed the association between one or more EDCs and the prevalence of endometriosis. The types of EDCs, association and outcome, participant characteristics and confounding variables were extracted and analysed. Quality assessment was performed using standard criteria.ResultsIn total, 29 studies were included. Phthalate esters were positively associated with the prevalence of endometriosis. The majority (71%) of studies revealed a significant association between bisphenol A, organochlorinated environmental pollutants (dioxins, dioxin-like compounds, organochlorinated pesticides, polychlorinated biphenyls) and the prevalence of endometriosis. A positive association between copper, chromium and prevalence of endometriosis was demonstrated in one study only. Cadmium, lead and mercury were not associated with the prevalence of endometriosis. There were conflicting results for the association between nickel and endometriosis. The relationship of EDCs and severity of endometriosis was not established in the studies.ConclusionWe found some evidence to suggest an association between phthalate esters, bisphenol A, organochlorinated environmental pollutants and the prevalence of endometriosis. Disentangling these exposures from various other factors that affect endometriosis is complex, but an important topic for further research.

Participation of Critical Residues from the Extreme C-Terminal End of the Human Androgen Receptor in the Ligand Binding Function†

Biochemistry ◽  
2001 ◽  
Vol 40 (29) ◽  
pp. 8431-8437 ◽  
Author(s):  
Bouchra Tahiri ◽  
Gilles Auzou ◽  
Jean-Claude Nicolas ◽  
Charles Sultan ◽  
Brigitte Lupo
Keyword(s):  
Androgen Receptor ◽  
Ligand Binding ◽  
Binding Function ◽  
Critical Residues ◽  
Human Androgen Receptor

The androgen receptor depends on ligand‐binding domain dimerization for transcriptional activation

EMBO Reports ◽  
2021 ◽  
Author(s):  
Sarah El Kharraz ◽  
Vanessa Dubois ◽  
Martin E Royen ◽  
Adriaan B Houtsmuller ◽  
Ekatarina Pavlova ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Ligand Binding ◽  
Transcriptional Activation ◽  
Binding Domain ◽  
Ligand Binding Domain

scholarly journals Endocrine Disrupting Action of Environmental Chemicals on Mammals

1999 ◽  
Vol 48 (5) ◽  
pp. 431-437,503
Author(s):  
Mutsuko KOIZUMI ◽  
Ryuichi HASEGAWA
Keyword(s):  
Environmental Chemicals ◽  
Endocrine Disrupting
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