Review
Biochemistry & Molecular Biology
Shafi Ullah Khan, Nafees Ahemad, Lay-Hong Chuah, Rakesh Naidu, Thet Thet Htar
Summary: G protein-coupled receptors (GPCRs) are the largest family of protein targets, with at least 500 members being therapeutic targets. G protein-coupled estrogen receptor-1 (GPER-1) has the ability in estrogen signaling and is considered a potential therapeutic target for estrogen-based cancers and other non-communicable diseases. However, the progress in understanding the structure and function of GPER-1 has been slow due to the limited availability of selective GPER-1 modulators.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Review
Cell Biology
Richard A. Pepermans, Geetanjali Sharma, Eric R. Prossnitz
Summary: Estrogen plays crucial roles in various cancers, metabolism, and immune regulation. The G protein-coupled estrogen receptor (GPER) has been found to contribute to endocrine therapy resistance in breast cancer and has potential therapeutic value in targeting other diseases such as obesity and diabetes. Ongoing clinical trials are exploring the use of GPER-selective agonists like G-1 in combination with immune checkpoint inhibition for cancer treatment.
Review
Pharmacology & Pharmacy
Jeffrey B. Arterburn, Eric R. Prossnitz
Summary: The actions of estrogens and related estrogenic molecules are complex and multifaceted in both sexes. These molecules target pathways that produce and respond to estrogens, and multiple receptors are involved in the responses. In particular, the G protein-coupled estrogen receptor (GPER) plays important roles in physiological responses to estrogenic compounds and has therapeutic implications for various diseases.
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Fujie Xu, Jipeng Ma, Xiaowu Wang, Xiaoya Wang, Weiyi Fang, Jingwei Sun, Zilin Li, Jincheng Liu
Summary: This article summarizes the function, tissue localization, ligands, and signaling pathways of GPER in different physiological and diseased conditions. It emphasizes the role of GPER in vascular pathology and physiology and presents evidence of GPER as a promising therapeutic target in hypertension, pulmonary hypertension, and atherosclerosis.
Review
Pharmacology & Pharmacy
Shaojie Yang, Zhe Yin, Guoqi Zhu
Summary: This review discusses the role of GPER in aging-related diseases, including vascular and neurological disorders. Activation of GPER has been found to improve cognitive function in the aging brain, with mechanisms different from other estrogen receptors. The review also carefully describes the molecular mechanisms underlying GPER-mediated effects.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Dermatology
Perihan Ozturk, Ergul Belge Kurutas, Mine Mujde Kus
Summary: This study found significantly increased serum GPER-1 levels in AGA patients, suggesting that GPER-1 may play a role in AGA pathogenesis independent from gender.
ARCHIVES OF DERMATOLOGICAL RESEARCH
(2022)
Article
Biology
Jing Xu, Jing Bai, Fujia Gao, Chao Xu, Yuanyuan Huang, Danyang Li, Lu Wang, Ruimin Wang
Summary: The study explores the role of G-protein-coupled estrogen receptor 1 (GPER1) signaling in regulating the early inflammatory process after global cerebral ischemia. The findings suggest that GPER1 signaling reduces pro-inflammatory signals and enhances anti-inflammatory signals in the brain. Brain-derived estrogen is found to mediate the anti-inflammatory effects of GPER1 signaling. Understanding the early-stage regulation of inflammation after global cerebral ischemia could lead to improved therapies for brain protection and outcomes.
Article
Neurosciences
Xiaoyu Li, Sonja Johann Gabriele M. Rune, Roland A. Bender
Summary: The membrane-bound receptor GPER1 plays a role in structural plasticity in the CA1 SLM, but its effects are sex-specific in the developing hippocampus. Activation of GPER1 with G1 increased spine density in organotypic cultures from female mice, while E2 showed a similar sex-specific effect on spine density. However, this increase in spine density did not lead to a corresponding increase in spine synapse density in the culture model.
Review
Cell Biology
Keith A. Hall, Edward J. Filardo
Summary: Estrogens play a crucial role in the pathogenesis of various cancers, especially in relation to environmental estrogens and GPER receptors. However, the current antiestrogen therapy for breast cancer does not consider these factors, indicating the need for a more holistic approach, such as targeting GPER receptors.
Article
Physiology
Nathalie Tristao Banhos Delgado, Wender do Nascimento Rouver, Leandro Ceotto Freitas-Lima, Ildernandes Vieira-Alves, Virginia Soares Lemos, Roger Lyrio dos Santos
Summary: The study reveals that the GPER agonist G-1 can induce a similar relaxing response in mesenteric arteries from hypertensive rats of both sexes, with differential involvement of endothelial mediators between males and females.
FRONTIERS IN PHYSIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Aliyu Muhammad, Gilead Ebiegberi Forcados, Abdurrahman Pharmacy Yusuf, Murtala Bello Abubakar, Idris Zubairu Sadiq, Isra Elhussin, Md. Abu Talha Siddique, Suleiman Aminu, Rabiatu Bako Suleiman, Yakubu Saddeeq Abubakar, Babangida Sanusi Katsayal, Clayton C. C. Yates, Sunila Mahavadi
Summary: This review critically examines the role of G-protein-coupled estrogen receptor (GPER) in diabetes mellitus and malignancy, highlighting the potential for GPER as a therapeutic target for management of these diseases. The expression patterns of GPER in diabetic models are currently lacking, while in various malignancies the expression of GPER appears to be complex and debatable. Further research is needed to investigate the expression patterns of GPER and its relationship with signaling pathways in diabetes mellitus and various malignancies.
Article
Reproductive Biology
Dong-Dong Gao, Chong-Feng Lan, Xiao-Nian Cao, Lei Chen, Tian-Lun Lei, Lei Peng, Jia-Wen Xu, Zhuo-Er Qiu, Long-Long Wang, Qing Sun, Zi-Yang Huang, Yun-Xin Zhu, Wen-Liang Zhou, Yi-Lin Zhang
Summary: In this study, it was found that GPER is expressed at the acrosome and mid-flagellum of mouse sperm. Activation of GPER triggers an increase in intracellular Ca2+ concentration in mouse sperm through PLC-dependent Ca2+ mobilization and CatSper-mediated Ca2+ influx, which promotes the acrosome reaction of mouse sperm.
BIOLOGY OF REPRODUCTION
(2022)
Article
Biochemistry & Molecular Biology
Alex Hirtz, Yann Bailly, Fabien Rech, Julien Pierson, Helene Dumond, Helene Dubois-Pot-Schneider
Summary: Glioblastoma is a common primary brain tumor with poor treatment outcomes. High expression of GPER1 is associated with better survival, suggesting the protective role of estrogen signaling. The G-1 agonist demonstrates anti-tumor effects on GBM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Liliana Torres-Lopez, Miguel Olivas-Aguirre, Kathya Villatoro-Gomez, Oxana Dobrovinskaya
Summary: G-1 can induce cytotoxicity, cell cycle arrest, reduced viability, and apoptosis in acute T-cell lymphoblastic leukemia cell lines. The rise of intracellular Ca2+ and destabilization of microtubules are important factors in the cytotoxic effects of G-1.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Neurosciences
Kyle Pemberton, Martina Rosato, Cass Dedert, Chelsea DeLeon, Christopher Arnatt, Fenglian Xu
Summary: Estrogen plays important roles in nervous system development and function. The activation of GPER has differential effects on rat hippocampal and cortical neurons, with a stronger response observed in hippocampal neurons. The GPER-mediated increase in Ca2+ in hippocampal neurons involves both the release of intracellular Ca2+ stores and the entry of extracellular Ca2+ through Ca2+ channels.
Article
Immunology
Angel S. Byrd, Xian M. O'Brien, Sonia S. Laforce-Nesbitt, Valentina E. Parisi, Matthew P. Hirakawa, Joseph M. Bliss, Jonathan S. Reichner
JOURNAL OF INFECTIOUS DISEASES
(2016)
Article
Neurosciences
Elizabeth M. Waters, Louisa I. Thompson, Parth Patel, Andreina D. Gonzales, Hector (Zhiyu) Ye, Edward J. Filardo, Deborah J. Clegg, Jolanta Gorecka, Keith T. Akama, Bruce S. McEwen, Teresa A. Milner
JOURNAL OF NEUROSCIENCE
(2015)
Article
Cell Biology
H. M. Gaudet, S. B. Cheng, E. M. Christensen, E. J. Filardo
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2015)
Article
Immunology
Courtney M. Johnson, Xian M. O'Brien, Angel S. Byrd, Valentina E. Parisi, Alex J. Loosely, Wei Li, Hadley Witt, Hafeez M. Faridi, Craig T. Lefort, Vineet Gupta, Minsoo Kim, Jonathan S. Reichner
JOURNAL OF IMMUNOLOGY
(2017)
Article
Immunology
Bethany M. Biron, Chun-Shiang Chung, Yaping Chen, Zachary Wilson, Eleanor A. Fallon, Jonathan S. Reichner, Alfred Ayala
JOURNAL OF IMMUNOLOGY
(2018)
Review
Biochemistry & Molecular Biology
Edward J. Filardo
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2018)
Review
Biochemistry & Molecular Biology
Matthias Barton, Edward J. Filardo, Stephen J. Lolait, Peter Thomas, Marcello Maggiolini, Eric R. Prossnitz
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2018)
Article
Endocrinology & Metabolism
Anne Almey, Elizabeth Cannell, Kyla Bertram, Edward Filardo, Teresa A. Milner, Wayne G. Brake
Article
Biochemistry & Molecular Biology
Jennet Toyjanova, Estefany Flores-Cortez, Jonathan S. Reichner, Christian Franck
JOURNAL OF BIOLOGICAL CHEMISTRY
(2015)
Article
Immunology
Alfred Ayala, Gwendolyn F. Elphick, Ye Sul Kim, Xin Huang, Arnaldo Carreira-Rosario, Sadella C. Santos, Nicholas J. Shubin, Yaping Chen, Jonathan Reichner, Chun-Shiang Chung
JOURNAL OF INNATE IMMUNITY
(2014)
Article
Cell Biology
Shi-Bin Cheng, Jing Dong, Yefei Pang, Jessica LaRocca, Mary Hixon, Peter Thomas, Edward J. Filardo
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2014)
Article
Multidisciplinary Sciences
Alex J. Loosley, Xian M. O'Brien, Jonathan S. Reichner, Jay X. Tang
Review
Endocrinology & Metabolism
Milad Rouhimoghadam, Anh S. Lu, Aliasger K. Salem, Edward J. Filardo
FRONTIERS IN ENDOCRINOLOGY
(2020)
Article
Medicine, Research & Experimental
Anh S. Lu, Milad Rouhimoghadam, Christopher K. Arnatt, Edward J. Filardo, Aliasger K. Salem
Summary: Decisions for hormonal therapy in breast cancer are based solely on ER presence, yet GPER is crucial. New chimeras UI-EP001 and UI-EP002 effectively degrade ERs and GPER, inducing cytotoxicity and cell cycle arrest in breast cancer cells. Targeting both plasma membrane and intracellular estrogen receptors could be a promising strategy for breast cancer treatment.
MOLECULAR PHARMACEUTICS
(2021)