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Review
. 2022 Aug 18:13:839005.
doi: 10.3389/fendo.2022.839005. eCollection 2022.

Role of estrogen receptors in health and disease

Peng Chen  1 , Bo Li  1 , Ling Ou-Yang  1
Affiliations
Review

Role of estrogen receptors in health and disease

Peng Chen et al. Front Endocrinol (Lausanne). .

Abstract

Estrogen receptors (ERs) regulate multiple complex physiological processes in humans. Abnormal ER signaling may result in various disorders, including reproductive system-related disorders (endometriosis, and breast, ovarian, and prostate cancer), bone-related abnormalities, lung cancer, cardiovascular disease, gastrointestinal disease, urogenital tract disease, neurodegenerative disorders, and cutaneous melanoma. ER alpha (ERα), ER beta (ERβ), and novel G-protein-coupled estrogen receptor 1 (GPER1) have been identified as the most prominent ERs. This review provides an overview of ERα, ERβ, and GPER1, as well as their functions in health and disease. Furthermore, the potential clinical applications and challenges are discussed.

Keywords: G-protein-coupled estrogen receptor 1; estrogen receptor alpha; estrogen receptor beta; mediation; signaling pathway.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Structure of estrogen receptors (ERs). Six structural and functional domains are highlighted: A, B domain (amino-terminal or NH2-terminal domain [NTD], activation function 1 [AF1]); C domain (DNA binding domain [DBD]); D domain (hinge region connecting the C and E domain); E, F domain (carboxyl- or COOH-terminal, ligand-binding domain [LBD], AF2).
Figure 2
Figure 2
Estrogen receptor alpha (ERα) isoforms. Six structural and functional domains are highlighted: A, B domain (amino- or NH2-terminal domain [NTD], AF1), C domain (DNA binding domain [DBD]), D domain (hinge region connecting the C and E domain), E, F domain (carboxyl- or COOH-terminal, ligand-binding domain [LBD], AF2).
Figure 3
Figure 3
Estrogen receptor beta (ERβ) isoforms. Six structural and functional domains are highlighted: A, B domain (amino- or NH2-terminal domain [NTD], AF1), C domain (DNA binding domain [DBD]), D domain (hinge region connecting the C and E domain), E, F domain (carboxyl- or COOH-terminal, ligand-binding domain [LBD], AF2).
Figure 4
Figure 4
Structures of G-protein-coupled estrogen receptor 1 (GPER1).
Figure 5
Figure 5
Estrogen signaling pathways. Estrogen or E2 (orange circle E in the graph) binds to the ERα/ERβ and GPER1, exerting its genomic and non-genomic effects. The genomic effect is shown in orange: the E2-receptor complex binds to EREs upon entry into the nucleus. The non-genomic effect is shown in blue: E2 binds to ERs in the membrane-like GPER1 and regulates the expression by modulating the ion channel opening or activation of related enzymes. E, estrogen or E2; ERα, estrogen receptor alpha; ERβ, estrogen receptor beta; GPER1, G protein-coupled estrogen receptor 1; ERE, estrogen response elements; PI3K, phosphatidylinositol 3-kinase; MAPK, mitogen-activated protein kinase.
Figure 6
Figure 6
The multifaceted role of ERs in various diseases.
See this image and copyright information in PMC

References

    1. Fuentes N, Silveyra P. Estrogen receptor signaling mechanisms. Adv Protein Chem Struct Biol (2019) 116:135–70. doi: 10.1016/bs.apcsb.2019.01.001 - DOI - PMC - PubMed
    1. Faltas CL, LeBron KA, Holz MK. Unconventional estrogen signaling in health and disease. Endocrinology (2020) 161(4):1–7. doi: 10.1210/endocr/bqaa030 - DOI - PMC - PubMed
    1. Tang ZR, Zhang R, Lian ZX, Deng SL, Yu K. Estrogen-receptor expression and function in female reproductive disease. Cells (2019) 8(10):1123–38. doi: 10.3390/cells8101123 - DOI - PMC - PubMed
    1. Flasch M, Bueschl C, Del Favero G, Adam G, Schuhmacher R, Marko D, et al. Elucidation of xenoestrogen metabolism by non-targeted, stable isotope-assisted mass spectrometry in breast cancer cells. Environ Int (2022) 158:106940. doi: 10.1016/j.envint.2021.106940 - DOI - PubMed
    1. Ohta K, Chiba Y, Kaise A, Endo Y. Structure-activity relationship study of diphenylamine-based estrogen receptor (ER) antagonists. Bioorg Med Chem (2015) 23(4):861–7. doi: 10.1016/j.bmc.2014.12.022 - DOI - PubMed