For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
8
views
57
references
 Top references
cited by
4
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      128
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Reconsidering the roles of endogenous estrogens and xenoestrogens: the membrane estradiol receptor G protein-coupled receptor 30 (GPR30) mediates the effects of various estrogens

      editorial

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Estrone (E1) and estriol (E3) are considered “weak” estrogens, which exert suppressive effects through estrogen receptors α and β. However, recent studies have demonstrated that E1 and E3, as well as estradiol (E2), suppress gonadotropin-releasing hormone-induced luteinizing hormone secretion from bovine gonadotrophs via G-protein-coupled receptor 30, which is expressed in various reproductive organs. Currently, there is a lack of fundamental knowledge regarding E1 and E3, including their blood levels. In addition, xenoestrogens may remain in the body over long time periods because of enterohepatic circulation. Therefore, it is time to reconsider the roles of endogenous estrogens and xenoestrogens for reproduction.

          Related collections

          Most cited references57

          • Record: found
          • Abstract: found
          • Article: not found

          Binding and activation of the seven-transmembrane estrogen receptor GPR30 by environmental estrogens: a potential novel mechanism of endocrine disruption.

          Jing-Jing Dong, Peter Thomas (2006)
          A wide variety of environmental contaminants have been shown to exert estrogenic actions in wildlife and laboratory animals through binding to nuclear estrogen receptors (ERs) and subsequent transcription of estrogen responsive genes. We show here that several of these environmental estrogens also bind to the novel seven-transmembrane estrogen receptor, GPR30, to activate alternative estrogen signaling pathways in an ER-negative cell line (HEK293) stably transfected with the receptor. Genestein was the most effective competitor for the receptor (IC(50) 133 nM), with a relative binding affinity (RBA) 13% that of estradiol-17beta (E2). Bisphenol A, zearalonone, and nonylphenol also had relatively high binding affinities for GPR30 with RBAs of 2-3%. Kepone, p,p'-DDT, 2,2',5',-PCB-4-OH and o,p'-DDE had lower affinities with RBAs of 0.25-1.3%, whereas o,p'-DDT, p,p'-DDE, methoxychlor and atrazine caused less than 50% displacement of [(3)H]-E2 at concentrations up to 10 microM. Overall, the binding affinities of these compounds for GPR30 are broadly similar to their affinities to the ERs. Environmental estrogens with relatively high binding affinities for GPR30 (genestein, bisphenol A, nonylphenol and Kepone) also displayed estrogen agonist activities in an in vitro assay of membrane-bound adenylyl cyclase activity, a GPR30-dependent signaling pathway activated by estrogens. The results indicate that nontraditional estrogen actions mediated through GPR30 are potentially susceptible to disruption by a variety of environmental estrogens.
          Article 0 comments Cited 150 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Identification of a GPER/GPR30 antagonist with improved estrogen receptor counterselectivity.

            Cristian Bologa, Tudor Oprea, Jeffrey Arterburn … (2011)
            GPER/GPR30 is a seven-transmembrane G protein-coupled estrogen receptor that regulates many aspects of mammalian biology and physiology. We have previously described both a GPER-selective agonist G-1 and antagonist G15 based on a tetrahydro-3H-cyclopenta[c]quinoline scaffold. The antagonist lacks an ethanone moiety that likely forms important hydrogen bonds involved in receptor activation. Computational docking studies suggested that the lack of the ethanone substituent in G15 could minimize key steric conflicts, present in G-1, that limit binding within the ERα ligand binding pocket. In this report, we identify low-affinity cross-reactivity of the GPER antagonist G15 to the classical estrogen receptor ERα. To generate an antagonist with enhanced selectivity, we therefore synthesized an isosteric G-1 derivative, G36, containing an isopropyl moiety in place of the ethanone moiety. We demonstrate that G36 shows decreased binding and activation of ERα, while maintaining its antagonist profile towards GPER. G36 selectively inhibits estrogen-mediated activation of PI3K by GPER but not ERα. It also inhibits estrogen- and G-1-mediated calcium mobilization as well as ERK1/2 activation, with no effect on EGF-mediated ERK1/2 activation. Similar to G15, G36 inhibits estrogen- and G-1-stimulated proliferation of uterine epithelial cells in vivo. The identification of G36 as a GPER antagonist with improved ER counterselectivity represents a significant step towards the development of new highly selective therapeutics for cancer and other diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.
            Article 0 comments Cited 92 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The unfolding stories of GPR30, a new membrane-bound estrogen receptor.

              Marcello Maggiolini, Didier Picard (2010)
              Steroid hormones such as estrogens are known to signal through ligand-regulated transcription factors of the nuclear receptor superfamily. In addition, they elicit rapid nongenomic responses from membrane-associated receptors. One of these receptors belongs to an entirely different family of proteins. The G protein-coupled and seven-transmembrane receptor, GPR30, is now widely recognized as an estrogen receptor (ER), hence its official new acronym GPER. It appears to mediate a wide range of responses to estrogen in a large variety of cell types. Its functions are clearly distinct from those of the classical nuclear ERs, although these pathways may overlap and interact in some cases. Here, we review the history of the discovery of this new ER, the evidence for the claim that it is an ER, its signal transduction, and its potential functions in physiology and disease.
              Article 0 comments Cited 92 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): J Reprod Dev
                Journal ID (iso-abbrev): J. Reprod. Dev
                Journal ID (publisher-id): JRD
                Title: The Journal of Reproduction and Development
                Publisher: The Society for Reproduction and Development
                ISSN (Print): 0916-8818
                ISSN (Electronic): 1348-4400
                Publication date (Electronic): 06 March 2018
                Publication date (Print): June 2018
                Volume: 64
                Issue: 3
                Pages: 203-208
                Affiliations
                [1) ]Faculty of Veterinary Medicine, Yamaguchi University, Yamaguchi 753-8515, Japan
                Author notes
                Correspondence: H Kadokawa (e-mail: hiroya@ 123456yamaguchi-u.ac.jp )
                Article
                Publisher ID: 2017-153
                DOI: 10.1262/jrd.2017-153
                PMC ID: 6021614
                PubMed ID: 29515057
                SO-VID: 57f587e2-d6bd-4e20-9bdc-8b9009e73557
                Copyright © ©2018 Society for Reproduction and Development
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License. (CC-BY-NC-ND 4.0: https://creativecommons.org/licenses/by-nc-nd/4.0/)

                History
                Date received : 07 December 2017
                Date accepted : 21 February 2018
                Categories
                Subject: Opinions and Hypotheses

                Keywords: gonadotroph,g protein-coupled estrogen receptor-1,pituitary,xenoestrogen,zearalenone
                Data availability:
                Keywords: gonadotroph, g protein-coupled estrogen receptor-1, pituitary, xenoestrogen, zearalenone

                Comments

                Comment on this article

                scite_

                Similar content128

                See all similar

                Cited by4

                See all cited by

                Most referenced authors385

                See all reference authors