Biological effects of xenoestrogens and the functional mechanisms via genomic and nongenomic pathways

2017 ◽  
Vol 25 (3) ◽  
pp. 306-322 ◽  
Author(s):  
Zhi-Xiang Xu ◽  
Jun Liu ◽  
Li-Peng Gu ◽  
Bin Huang ◽  
Xue-Jun Pan
Keyword(s):  
Estrogen Receptor ◽  
Estrogen Receptor Alpha ◽  
Biological Effects ◽  
Receptor Alpha ◽  
Estrogenic Effects ◽  
Immunological Effects ◽  
Functional Mechanisms ◽  
Nongenomic Effects ◽  
G Protein Coupled ◽  
Insight Into

Xenoestrogens (XEs) are a class of substances that exert estrogenic effects by mimicking or blocking endogenous hormones. The sources, environmental behavior, and fate of typical XEs are described. XEs’ adverse developmental, metabolic, and immunological effects are then presented with respect to reproductive functions. The mechanisms underlying XEs’ genomic and nongenomic effects are reviewed. XEs can alter gene transcription by interfering with the functioning of conventional estrogen receptors, but they are also capable of activating multiple kinase signaling pathways that disrupt membrane-associated receptors, such as estrogen receptor alpha-36 (ERα36), estrogen receptor alpha-46 (ERα46), and G protein-coupled receptor 30 (GPR30). This review aims to provide insight into XEs’ environmental effects and to explore the prevention and treatment of their estrogenic effects based on sufficient comprehension of the mechanisms involved.

scholarly journals Estrogen receptor alpha mediates neuronal differentiation and neuroprotection in PC12 cells: critical role of the A/B domain of the receptor

2005 ◽  
Vol 35 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Yohann Mérot ◽  
François Ferrière ◽  
Edith Debroas ◽  
Gilles Flouriot ◽  
Dominique Duval ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Neuronal Differentiation ◽  
Pc12 Cells ◽  
Estrogen Receptor Alpha ◽  
Transcriptional Activity ◽  
Target Genes ◽  
Critical Role ◽  
Full Length ◽  
Receptor Alpha ◽  
Estrogenic Effects

Numerous studies, both in vivo and in vitro, have reported neuronal differentiating and neuroprotective actions of estrogens. Most of these estrogenic effects are mediated through specific receptors termed estrogen receptors. The aim of this study was to assess the importance of the N-terminal A/B domain of the estrogen receptor-alpha (ERα) in its neuronal aspects. Consequently, estrogen effects on (i) the transcriptional activity of target genes, (ii) neuronal differentiation and (iii) neuroprotection in PC12 cells transfected with either a full length form of ERα or an A/B domain truncated form (ERαCF), have been studied. We demonstrate that the maximal estrogen-induced transcriptional activity of reporter genes requires a full length ERα, especially when cells are differentiated. Precisely, the transcriptional activity of ERα in differentiated cells relies, predominantly, on the activation function AF-1, located in the A/B domain. Furthermore, in PC12 cells stably expressing ERα, 17β-estradiol markedly enhances the neurite outgrowth triggered by treatment with nerve growth factor and protects cells from oxidative shocks induced by depletion of glutathione. These estrogenic effects are not observed in non-transfected cells and in cells transfected with the truncated ER, devoid of the A/B domain. Altogether, these results underline the importance of the A/B domain of ERα in both the differentiating and the neuroprotective effects of estrogens.

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