Extranuclear-initiated estrogenic actions of endocrine disrupting chemicals: Is there toxicology beyond paracelsus?
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Title: | Extranuclear-initiated estrogenic actions of endocrine disrupting chemicals: Is there toxicology beyond paracelsus? |
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Authors: | Nadal, Ángel | Fuentes, Esther | Ripoll, Cristina | Villar-Pazos, Sabrina | Castellano-Muñoz, Manuel | Soriano, Sergi | Martinez-Pinna, Juan | Quesada, Iván | Alonso Magdalena, Paloma |
Research Group/s: | Fisiología Neuroendocrina (FINE) |
Center, Department or Service: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología |
Keywords: | Endocrine disruptors | Beta-cells | Islet of Langerhans | Estrogen receptors | Bisphenol-A | Bisphenol-S |
Knowledge Area: | Fisiología |
Issue Date: | Feb-2018 |
Publisher: | Elsevier |
Citation: | The Journal of Steroid Biochemistry and Molecular Biology. 2018, 176: 16-22. doi:10.1016/j.jsbmb.2017.01.014 |
Abstract: | Endocrine Disrupting Chemicals (EDCs), including bisphenol-A (BPA) do not act as traditional toxic chemicals inducing massive cell damage or death in an unspecific manner. EDCs can work upon binding to hormone receptors, acting as agonists, antagonists or modulators. Bisphenol-A displays estrogenic activity and, for many years it has been classified as a weak estrogen, based on the classic transcriptional action of estrogen receptors serving as transcription factors. However, during the last two decades our knowledge about estrogen signaling has advanced considerably. It is now accepted that estrogen receptors ERα and ERβ activate signaling pathways outside the nucleus which may or may not involve transcription. In addition, a new membrane estrogen receptor, GPER, has been proposed. Pharmacological and molecular evidence, along with results obtained in genetically modified mice, demonstrated that BPA, and its substitute BPS, are potent estrogens acting at nanomolar concentrations via extranuclear ERα, ERβ, and GPER. The different signaling pathways activated by BPA and BPS explain the well-known estrogenic effects of low doses of EDCs as well as non-monotonic dose-response relationships. These signaling pathways may help to explain the actions of EDCs with estrogenic activity in the etiology of different pathologies, including type-2 diabetes and obesity. |
Sponsor: | The author laboratories are funded by the Ministerio de Economía y Competitividad (SAF2014-58335-P and BFU2013-42789-P) and Generalitat Valenciana (PROMETEOII/2015/016). CIBERDEM is an initiative of the Instituto de Salud Carlos III. |
URI: | http://hdl.handle.net/10045/71535 |
ISSN: | 0960-0760 (Print) | 1879-1220 (Online) |
DOI: | 10.1016/j.jsbmb.2017.01.014 |
Language: | eng |
Type: | info:eu-repo/semantics/article |
Rights: | © 2017 Elsevier Ltd. |
Peer Review: | si |
Publisher version: | http://dx.doi.org/10.1016/j.jsbmb.2017.01.014 |
Appears in Collections: | INV - FINE - Artículos de Revistas |
Files in This Item:
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2018_Nadal_etal_JSBMB_final.pdf | Versión final (acceso restringido) | 581,52 kB | Adobe PDF | Open Request a copy |
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