scholarly journals Importance of Receptor Conformations in Docking Calculation-Based Risk Assessment for Endocrine Disruptors against Estrogen Receptor α

ACS Omega ◽  
2019 ◽  
Vol 4 (4) ◽  
pp. 6620-6629 ◽  
Author(s):  
Hitoshi Kesamaru ◽  
Keitaro Suyama ◽  
Takeru Nose
Keyword(s):  
Risk Assessment ◽  
Estrogen Receptor ◽  
Endocrine Disruptors ◽  
Estrogen Receptor Α ◽  
Docking Calculation

scholarly journals Association of Cryptorchidism with a Specific Haplotype of the Estrogen Receptor α Gene: Implication for the Susceptibility to Estrogenic Environmental Endocrine Disruptors

2005 ◽  
Vol 90 (8) ◽  
pp. 4716-4721 ◽  
Author(s):  
Rie Yoshida ◽  
Maki Fukami ◽  
Isoji Sasagawa ◽  
Tomonobu Hasegawa ◽  
Naoyuki Kamatani ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Endocrine Disruptors ◽  
Outcome Measure ◽  
Estrogen Receptor Α ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Main Outcome Measure ◽  
Environmental Endocrine Disruptors ◽  
Estrogenic Effects ◽  
Specific Haplotype

Context: The prevalence of cryptorchidism (CO) has increased during the past few decades in several countries, and this event has primarily been ascribed to the estrogenic effects of environmental endocrine disruptors (EEDs). Little is known, however, about the role of genetic susceptibility to EEDs in this phenomenon. Objective: The objective of this study was to determine whether CO is associated with a specific haplotype of the gene for estrogen receptor α (ESR1) that mediates the estrogenic effects of EEDs. Design: This was a case-control study. Setting: The study was performed at the National Research Institute and University Hospitals. Subjects: Sixty-three cryptorchid males, aged 1–13 yr, and 47 control males, aged 4–12 yr, were studied. Intervention: After genotyping 15 single nucleotide polymorphisms widely distributed in the greater than 300-kb genomic sequences of ESR1, haplotype analysis was performed. Main Outcome Measure: Identification of a specific ESR1 haplotype associated with CO was the main outcome measure. Results: A haplotype block was identified for an approximately 50-kb region encompassing single nucleotide polymorphisms 10–14 in the 3′ region of ESR1 in both groups. The frequency of the estimated AGATA haplotype within the block was higher in the patients than in the control males (34.0% vs. 21.3%; P = 0.037), and the association of this haplotype with CO phenotype was significant in a recessive mode (P = 0.0060). The homozygosity for this haplotype was identified only in the patients, and the frequency of the homozygotes was significantly different between the two groups (10 of 63 vs. zero of 47; P = 0.0042). Conclusions: The association of CO with homozygosity for the specific ESR1 haplotype suggests the relevance of genetic susceptibility to EEDs in the development of CO.

scholarly journals The promiscuous estrogen receptor: evolution of physiological estrogens and response to phytochemicals and endocrine disruptors

2017 ◽  
Author(s):  
Michael E. Baker ◽  
Richard Lathe
Keyword(s):  
Estrogen Receptor ◽  
Endocrine Disruptors ◽  
Estrogenic Activity ◽  
Structural Diversity ◽  
Estrogen Receptor Α ◽  
Industrial Chemicals ◽  
Reproductive Tissues ◽  
Synthetic Chemicals ◽  
Phenolic Group

ABSTRACTMany actions of estradiol (E2), the principal physiological estrogen in vertebrates, are mediated by estrogen receptor-α (ERα) and ERβ. An important physiological feature of vertebrate ERs is their promiscuous response to several physiological steroids, including estradiol (E2), Δ5-androstenediol, 5α-androstanediol, and 27-hydroxycholesterol. A novel structural characteristic of Δ5-androstenediol, 5α-androstanediol, and 27-hydroxycholesterol is the presence of a C19 methyl group, which precludes the presence of an aromatic A ring with a C3 phenolic group that is a defining property of E2. The structural diversity of these estrogens can explain the response of the ER to synthetic chemicals such as bisphenol A and DDT, which disrupt estrogen physiology in vertebrates, and the estrogenic activity of a variety of plant-derived chemicals such as genistein, coumestrol, and resveratrol. Diversity in the A ring of physiological estrogens also expands potential structures of industrial chemicals that can act as endocrine disruptors. Compared to E2, synthesis of 27-hydroxycholesterol and Δ5-androstenediol is simpler, leading us, based on parsimony, to propose that one or both of these steroids or a related metabolite was a physiological estrogen early in the evolution of the ER, with E2 assuming this role later as the canonical estrogen. In addition to the well-studied role of the ER in reproductive physiology, the ER also is an important transcription factor in non-reproductive tissues such as the cardiovascular system, kidney, bone, and brain. Some of these ER actions in non-reproductive tissues appeared early in vertebrate evolution, long before mammals evolved.

1322: The Expression of Estrogen Receptor α and Estrogen Receptor β in the Human Fetal Prostate

2004 ◽  
Vol 171 (4S) ◽  
pp. 348-348
Author(s):  
Ellen Shapiro ◽  
Hongying Huang ◽  
Rachael R. Mash ◽  
Eliza Ng ◽  
Deborah E. McFadden ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Α ◽  
Estrogen Receptor Β
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