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Molecular Pathways of Estrogen Receptor Action 2.0
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Molecular Pathways of Estrogen Receptor Action 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (31 May 2019) | Viewed by 13335

Special Issue Editor

Dr. Farzad Pakdel

E-Mail Website
Guest Editor
Research Institute in Health, Environment and Occupation (Irset), Inserm U1085, Transcription, Environment and Cancer Group, University of Rennes 1, 35000 Rennes, France
Interests: estrogen receptor; gene expression; transcription mechanisms; endocrine disrupter chemicals; breast cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is the continuation of our 2017 Special Issue, “Molecular Pathways of Estrogen Receptor Action” (https://0-www-mdpi-com.brum.beds.ac.uk/journal/ijms/special_issues/estrogen).

Estrogen Receptors (ERs), which belong to the nuclear receptor family, control a variety of physiological processes, including growth, development, and metabolism of reproductive and non-reproductive tissues. ERs are also intimately associated with several human pathologies, for instance, breast and ovarian cancers, osteoporosis, coronary or neurodegenerative diseases. The comprehension of the mechanisms underlining ER-mediated effects in these physiopathological processes is the main goal of this Special Issue. Notably, how do ERs control transcription and epigenetic regulations and interact with chromatin and cellular signaling pathways to regulate cell fate, such as proliferation, differentiation and apoptosis? What is the role of ligands, including environmental estrogens, in modulating genomic and non-genomic activity of ERs under normal and pathological conditions?

In order to provide a comprehensive overview of the molecular mechanisms of ERs, researchers are invited to submit original research, mini and full reviews for this Special Issue of the International Journal of Molecular Sciences, entitled “Molecular Pathways of Estrogen Receptor Action", which will cover a selection of topics, highlighting the key roles of ERs in health and disease.

Dr. Farzad Pakdel
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Estrogens and xenoestrogens
  • Selective Estrogen Receptor modulators
  • Ligand and cofactor interactions
  • Transcription
  • Epigenetics
  • Chromatin
  • Cell signaling
  • Cancer
  • Physiopathology

Related Special Issue

Published Papers (4 papers)

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Research

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18 pages, 4189 KiB  
Article
Sex- and Age-Related Estrogen Signaling Alteration in Inflammatory Bowel Diseases: Modulatory Role of Estrogen Receptors
by Damian Jacenik, Adam I. Cygankiewicz, Anna Mokrowiecka, Ewa Małecka-Panas, Jakub Fichna and Wanda M. Krajewska
Int. J. Mol. Sci. 2019, 20(13), 3175; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20133175 - 28 Jun 2019
Cited by 29 | Viewed by 3678
Abstract
The pathogenesis of inflammatory bowel diseases (IBD) seems to be associated with alterations of immunoregulation. Several lines of evidence suggest that estrogens play a role in the modulation of immune responses and may be related to the etiology of IBD. The purpose of [...] Read more.
The pathogenesis of inflammatory bowel diseases (IBD) seems to be associated with alterations of immunoregulation. Several lines of evidence suggest that estrogens play a role in the modulation of immune responses and may be related to the etiology of IBD. The purpose of this work was to examine the involvement of G protein-coupled estrogen receptor (GPER), estrogen receptor α (ERα), estrogen receptor β (ERβ) and ERα spliced variants ERα36 and ERα46 in Crohn’s disease (CD) and ulcerative colitis (UC). The studied group included 73 patients with IBD and 31 sex and age-related controls. No differences in serum levels of 17β-estradiol nor of CYP1A1 and SULT1E1 enzymes involved in estrogen catabolism were stated. The expression pattern of estrogen receptors in tissue samples was quantified using real-time PCR and Western blotting. Statistically significant up-regulation of GPER and ERα in both CD and UC as well as down-regulation of ERβ in CD patients was found. However, differences in the expression of estrogen receptors in CD and UC have been identified, depending on the sex and age of patients. In men, up-regulation of GPER, ERα and ERα46 expression was shown in CD and UC patients. In women under 50 years of age, GPER protein level increased in UC whereas ERβ expression tended to decrease in CD and UC patients. In turn, in women over 50 the protein level of ERα increased in UC while ERβ expression decreased in CD patients. Dysregulation of estrogen receptors in the intestinal mucosa of patients with CD and UC indicates that estrogen signaling may play a role in the local immune response and maintain epithelial homeostasis in a gender- and age-dependent manner. Full article
(This article belongs to the Special Issue Molecular Pathways of Estrogen Receptor Action 2.0)
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14 pages, 1066 KiB  
Article
Novel Selective Estrogen Receptor Modulator Ameliorates Murine Colitis
by Lauri Polari, Santeri Anttila, Terhi Helenius, Anu Wiklund, Tero Linnanen, Diana M. Toivola and Jorma Määttä
Int. J. Mol. Sci. 2019, 20(12), 3007; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20123007 - 20 Jun 2019
Cited by 8 | Viewed by 3095
Abstract
Estrogen-receptor-mediated signaling has been suggested to decrease the inflammatory response in monocyte macrophages. Previously, we showed that a novel selective estrogen receptor modulator (SERM2) promotes anti-inflammatory phenotype of monocytes in vitro. In this study, we demonstrate the potential of SERM2 in amelioration of [...] Read more.
Estrogen-receptor-mediated signaling has been suggested to decrease the inflammatory response in monocyte macrophages. Previously, we showed that a novel selective estrogen receptor modulator (SERM2) promotes anti-inflammatory phenotype of monocytes in vitro. In this study, we demonstrate the potential of SERM2 in amelioration of colitis. We utilized a dextran sodium sulfate (DSS)-induced colitis model in FVB/n mice to demonstrate the effects of orally administered SERM2 on the clinical status of the mice and the histopathological changes in the colon, as well as proportion of Mrc-1 positive macrophages. SERM2 nuclear receptor affinities were measured by radioligand binding assays. Orally administered, this compound significantly alleviated DSS-induced colitis in male mice and induced local estrogen receptor activation in the inflamed colon, as well as promoting anti-inflammatory cytokine expression and infiltration of anti-inflammatory monocytes. We show that this novel drug candidate has an affinity to estrogen receptors α and β and progesterone receptors, but not to glucocorticoid receptor, thus expressing unique binding properties compared to other sex steroid receptor ligands. These results indicate that novel drug candidates to alleviate inflammatory conditions of the colon could be found among sex steroid receptor activating compounds. Full article
(This article belongs to the Special Issue Molecular Pathways of Estrogen Receptor Action 2.0)
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16 pages, 4938 KiB  
Article
Rhododendrin-Induced RNF146 Expression via Estrogen Receptor β Activation is Cytoprotective Against 6-OHDA-Induced Oxidative Stress
by Hyojung Kim, Jisoo Park, HyunHee Leem, MyoungLae Cho, Jin-Ha Yoon, Han-Joo Maeng and Yunjong Lee
Int. J. Mol. Sci. 2019, 20(7), 1772; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20071772 - 10 Apr 2019
Cited by 12 | Viewed by 3285
Abstract
Ring finger protein 146 (RNF146) is an E3 ubiquitin ligase whose activity prevents poly (ADP-ribose) polymerase 1 (PARP1)-dependent neurodegeneration in Parkinson’s disease (PD). Previously, we reported that rhododendrin is a chemical inducer that increases RNF146 expression. However, the molecular mechanism of rhododendrin-induced RNF146 [...] Read more.
Ring finger protein 146 (RNF146) is an E3 ubiquitin ligase whose activity prevents poly (ADP-ribose) polymerase 1 (PARP1)-dependent neurodegeneration in Parkinson’s disease (PD). Previously, we reported that rhododendrin is a chemical inducer that increases RNF146 expression. However, the molecular mechanism of rhododendrin-induced RNF146 expression is largely unknown and its translational application for the treatment of Parkinson’s disease remains unexplored. Here we found that rhododendrin increased RNF146 expression via estrogen receptor β (ERβ) activation. Rhododendrin stimulated ERβ nuclear translocation and binding to the RNF146 promoter, thereby enhancing its transcription. Rhododendrin is cytoprotective against 6-hydroxydopamine (6-OHDA)-induced cell death, which is largely dependent on ERβ activity and RNF146 expression. Finally, we demonstrated that rhododendrin treatment resulted in RNF146 expression in dopaminergic neurons in mice. Moreover, dopaminergic neuron viability was markedly enhanced by pretreatment with rhododendrin in 6-OHDA-induced mouse models for PD. Our findings indicate that estrogen receptor activation plays a neuroprotective role and that rhododendrin could be a potential therapeutic agent in preventing PARP1-dependent dopaminergic cell loss in PD. Full article
(This article belongs to the Special Issue Molecular Pathways of Estrogen Receptor Action 2.0)
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Review

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12 pages, 994 KiB  
Review
Transactivation Function-1-Mediated Partial Agonist Activity of Selective Estrogen Receptor Modulator Requires Homo-Dimerization of the Estrogen Receptor α Ligand Binding Domain
by Yukitomo Arao and Kenneth S. Korach
Int. J. Mol. Sci. 2019, 20(15), 3718; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms20153718 - 30 Jul 2019
Cited by 5 | Viewed by 2857
Abstract
The isolation of estrogen receptor alpha (ERα) cDNA was successful around 30 years ago. The characteristics of ERα protein have been examined from various aspects, primarily through in vitro cell culture studies, but more recently using in vivo experimental models. There remains, however, [...] Read more.
The isolation of estrogen receptor alpha (ERα) cDNA was successful around 30 years ago. The characteristics of ERα protein have been examined from various aspects, primarily through in vitro cell culture studies, but more recently using in vivo experimental models. There remains, however, some uncharacterized ERα functionalities. In particular, the mechanism of partial agonist activity of selective estrogen receptor modulators (SERMs) that involves control of the N-terminal transcription function of ERα, termed AF-1, is still an unsolved ERα functionality. We review the possible mechanism of SERM-dependent regulation of ERα AF-1-mediated transcriptional activity, which includes the role of helix 12 of ERα ligand binding domain (LBD) for SERM-dependent AF-1 regulation. In addition, we describe a specific portion of the LBD that associates with blocking AF-1 activity with an additional role of the F-domain in mediating SERM activity. Full article
(This article belongs to the Special Issue Molecular Pathways of Estrogen Receptor Action 2.0)
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