Role of Estrogen Receptors in Health and Disease

Overview

Journal Front Endocrinol (Lausanne)

Specialty Endocrinology

Date 2022 Sep 5

PMID 36060947

Authors

Peng Chen

Bo Li

Ling Ou-Yang

Affiliations

Soon will be listed here.

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.

Citing Articles

The intersection of aging and estrogen in osteoarthritis.

Atasoy-Zeybek A, Showel K, Nagelli C, Westendorf J, Evans C NPJ Womens Health. 2025; 3(1):15.

PMID: 40017990 PMC: 11860234. DOI: 10.1038/s44294-025-00063-1.

Cellular Epigenetic Targets and Epidrugs in Breast Cancer Therapy: Mechanisms, Challenges, and Future Perspectives.

Alalhareth I, Alyami S, Alshareef A, Ajeibi A, Al Munjem M, Elfifi A Pharmaceuticals (Basel). 2025; 18(2).

PMID: 40006021 PMC: 11858621. DOI: 10.3390/ph18020207.

Methylation of ESRα Promoters in Benign Breast Tumors Could Be a Signature for Progression to Breast Cancer in African American Women.

Dasi S, Naab T, Kwabi-Addo B, Apprey V, Beyene D, Dewitty Jr R Cancer Genomics Proteomics. 2025; 22(2):208-230.

PMID: 39993808 PMC: 11880923. DOI: 10.21873/cgp.20497.

Novel role of general transcript factor IIH subunit 2 (GTF2H2) in the development and sex disparity of hepatocellular carcinoma.

Li Y, OuYang Q, Chen Z, Zhou D, Li Z, Yang X Oncogene. 2025; .

PMID: 39972070 DOI: 10.1038/s41388-025-03301-7.

17-beta estradiol prevents cardiac myocyte hypertrophy by regulating mitochondrial E3 ubiquitin ligase 1.

Calle X, Garrido-Moreno V, Becerra B, Troncoso M, Silva-Aguero J, Guajardo-Correa E Cell Death Dis. 2025; 16(1):111.

PMID: 39971924 PMC: 11839923. DOI: 10.1038/s41419-025-07389-3.

References

Faltas C, LeBron K, Holz M . Unconventional Estrogen Signaling in Health and Disease. Endocrinology. 2020; 161(4). PMC: 7101056. DOI: 10.1210/endocr/bqaa030. View

JENSEN E, Suzuki T, Numata M, Smith S, Desombre E . Estrogen-binding substances of target tissues. Steroids. 1969; 13(4):417-27. DOI: 10.1016/0039-128x(69)90053-1. View

Bessa A, Campos F, Videira R, Mendes-Oliveira J, Bessa-Neto D, Baltazar G . GPER: A new tool to protect dopaminergic neurons?. Biochim Biophys Acta. 2015; 1852(10 Pt A):2035-41. DOI: 10.1016/j.bbadis.2015.07.004. View

Marengo S, Chung L . An orthotopic model for the study of growth factors in the ventral prostate of the rat: effects of epidermal growth factor and basic fibroblast growth factor. J Androl. 1994; 15(4):277-86. View

Wang H, Sun X, Lin M, Ferrario C, Van Remmen H, Groban L . G protein-coupled estrogen receptor (GPER) deficiency induces cardiac remodeling through oxidative stress. Transl Res. 2018; 199:39-51. PMC: 6151279. DOI: 10.1016/j.trsl.2018.04.005. View

Cauley J . Estrogen and bone health in men and women. Steroids. 2015; 99(Pt A):11-5. DOI: 10.1016/j.steroids.2014.12.010. View

Mollerup S, Jorgensen K, Berge G, Haugen A . Expression of estrogen receptors alpha and beta in human lung tissue and cell lines. Lung Cancer. 2002; 37(2):153-9. DOI: 10.1016/s0169-5002(02)00039-9. View

Ciucci A, Zannoni G, Travaglia D, Petrillo M, Scambia G, Gallo D . Prognostic significance of the estrogen receptor beta (ERβ) isoforms ERβ1, ERβ2, and ERβ5 in advanced serous ovarian cancer. Gynecol Oncol. 2014; 132(2):351-9. DOI: 10.1016/j.ygyno.2013.12.027. View

Iorga A, Cunningham C, Moazeni S, Ruffenach G, Umar S, Eghbali M . The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biol Sex Differ. 2017; 8(1):33. PMC: 5655818. DOI: 10.1186/s13293-017-0152-8. View

10.

Ryu W, Kim J, Jang Y, Park S, Um J, Park S . Expression of estrogen receptors in gastric cancer and their clinical significance. J Surg Oncol. 2012; 106(4):456-61. DOI: 10.1002/jso.23097. View

11.

Wong N, Malcomson R, Jodrell D, Groome N, Harrison D, Saunders P . ERbeta isoform expression in colorectal carcinoma: an in vivo and in vitro study of clinicopathological and molecular correlates. J Pathol. 2005; 207(1):53-60. DOI: 10.1002/path.1807. View

12.

Langdon S, Herrington C, Hollis R, Gourley C . Estrogen Signaling and Its Potential as a Target for Therapy in Ovarian Cancer. Cancers (Basel). 2020; 12(6). PMC: 7352420. DOI: 10.3390/cancers12061647. View

13.

Zagni E, Simoni L, Colombo D . Sex and Gender Differences in Central Nervous System-Related Disorders. Neurosci J. 2016; 2016:2827090. PMC: 4904110. DOI: 10.1155/2016/2827090. View

14.

Lin L, Zhou M, Que R, Chen Y, Liu X, Zhang K . Saikosaponin-d protects against liver fibrosis by regulating the estrogen receptor-β/NLRP3 inflammasome pathway. Biochem Cell Biol. 2021; 99(5):666-674. DOI: 10.1139/bcb-2020-0561. View

15.

Fu Z, Wang X, Zhou H, Li Y, Chen Y, Wang Z . GRP78 positively regulates estrogen‑stimulated cell growth mediated by ER‑α36 in gastric cancer cells. Mol Med Rep. 2017; 16(6):8329-8334. DOI: 10.3892/mmr.2017.7615. View

16.

Taylor A, Al-Azzawi F . Immunolocalisation of oestrogen receptor beta in human tissues. J Mol Endocrinol. 2000; 24(1):145-55. DOI: 10.1677/jme.0.0240145. View

17.

Maggiolini M, Vivacqua A, Fasanella G, Grazia Recchia A, Sisci D, Pezzi V . The G protein-coupled receptor GPR30 mediates c-fos up-regulation by 17beta-estradiol and phytoestrogens in breast cancer cells. J Biol Chem. 2004; 279(26):27008-16. DOI: 10.1074/jbc.M403588200. View

18.

Torring N, Vinter-Jensen L, Pedersen S, Sorensen F, Flyvbjerg A, Nexo E . Systemic administration of insulin-like growth factor I (IGF-I) causes growth of the rat prostate. J Urol. 1997; 158(1):222-7. DOI: 10.1097/00005392-199707000-00075. View

19.

Hsu L, Liu K, Tsai M, Wu C, Feng A, Chu N . Estrogen adversely affects the prognosis of patients with lung adenocarcinoma. Cancer Sci. 2014; 106(1):51-9. PMC: 4317775. DOI: 10.1111/cas.12558. View

20.

Westphal C, Schubert C, Prelle K, Penkalla A, Fliegner D, Petrov G . Effects of estrogen, an ERα agonist and raloxifene on pressure overload induced cardiac hypertrophy. PLoS One. 2012; 7(12):e50802. PMC: 3515519. DOI: 10.1371/journal.pone.0050802. View