Regulation of Estrogen Receptor Beta Activity and Implications in Health and Disease

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2009 Aug 12

PMID 19669093

Citations 27

Authors

Elin Swedenborg

Krista A Power

Wen Cai

Ingemar Pongratz

Joelle Ruegg

Affiliations

Soon will be listed here.

Abstract

Together with the estrogen receptor (ER) alpha, estrogen receptor beta (ER beta ) mediates many of the physiological effects of estrogens. As ER beta is crucially involved in a variety of important physiological processes, its activity should be tightly regulated. ER beta regulation is achieved by hormone binding as well as by posttranslational modifications of the receptor. Furthermore, ER beta expression levels are under circadian control and can be regulated by DNA methylation of the ER beta promoter region. There are also a number of factors that can interfere with ER beta activity, such as phytoestrogens, endocrine disruptive chemicals, and growth factors. In this article, we outline different mechanisms of ER beta regulation and how they are implicated in various diseases. We also discuss how these insights might help to specifically target ER beta in drug design.

Citing Articles

Unanticipated differences in the rat plasma metabolome of genistein and daidzein.

Montoya G, van Ravenzwaay B, Seefelder W, Haake V, Kamp H Arch Toxicol. 2025; .

PMID: 39954026 DOI: 10.1007/s00204-025-03967-8.

Role of estrogen receptors in health and disease.

Chen P, Li B, Ou-Yang L Front Endocrinol (Lausanne). 2022; 13:839005.

PMID: 36060947 PMC: 9433670. DOI: 10.3389/fendo.2022.839005.

Y It Matters-Sex Differences in Fetal Lung Development.

Laube M, Thome U Biomolecules. 2022; 12(3).

PMID: 35327629 PMC: 8946560. DOI: 10.3390/biom12030437.

Estrogen Receptor Beta: The Promising Biomarker and Potential Target in Metastases.

Bozovic A, Mandusic V, Todorovic L, Krajnovic M Int J Mol Sci. 2021; 22(4).

PMID: 33562134 PMC: 7914503. DOI: 10.3390/ijms22041656.

The prognostic factors of recurrence and survival in female patients with lung adenocarcinoma and breast cancer.

Chen Y, Huang Y, Huang H, Chang H, Lee S, Shieh Y J Cancer Res Clin Oncol. 2020; 146(5):1299-1306.

PMID: 32107626 DOI: 10.1007/s00432-020-03162-5.

References

Driggers P, Segars J, Rubino D . The proto-oncoprotein Brx activates estrogen receptor beta by a p38 mitogen-activated protein kinase pathway. J Biol Chem. 2001; 276(50):46792-7. PMC: 4152864. DOI: 10.1074/jbc.M106927200. View

Seo H, DeNardo D, Jacquot Y, Laios I, Vidal D, Zambrana C . Stimulatory effect of genistein and apigenin on the growth of breast cancer cells correlates with their ability to activate ER alpha. Breast Cancer Res Treat. 2006; 99(2):121-34. DOI: 10.1007/s10549-006-9191-2. View

Safe S, Wormke M . Inhibitory aryl hydrocarbon receptor-estrogen receptor alpha cross-talk and mechanisms of action. Chem Res Toxicol. 2003; 16(7):807-16. DOI: 10.1021/tx034036r. View

Noren K, Meironyte D . Certain organochlorine and organobromine contaminants in Swedish human milk in perspective of past 20-30 years. Chemosphere. 2000; 40(9-11):1111-23. DOI: 10.1016/s0045-6535(99)00360-4. View

Welshons W, Nagel S, Vom Saal F . Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinology. 2006; 147(6 Suppl):S56-69. DOI: 10.1210/en.2005-1159. View

Rutherford T, Brown W, Sapi E, Aschkenazi S, Munoz A, Mor G . Absence of estrogen receptor-beta expression in metastatic ovarian cancer. Obstet Gynecol. 2000; 96(3):417-21. DOI: 10.1016/s0029-7844(00)00917-0. View

Picard N, Charbonneau C, Sanchez M, Licznar A, Busson M, Lazennec G . Phosphorylation of activation function-1 regulates proteasome-dependent nuclear mobility and E6-associated protein ubiquitin ligase recruitment to the estrogen receptor beta. Mol Endocrinol. 2007; 22(2):317-30. PMC: 2346536. DOI: 10.1210/me.2007-0281. View

Cappelletti V, Saturno G, Miodini P, Korner W, Daidone M . Selective modulation of ER-beta by estradiol and xenoestrogens in human breast cancer cell lines. Cell Mol Life Sci. 2003; 60(3):567-76. PMC: 11138679. DOI: 10.1007/s000180300048. View

Allred C, Allred K, Ju Y, Virant S, Helferich W . Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res. 2001; 61(13):5045-50. View

10.

Foryst-Ludwig A, Clemenz M, Hohmann S, Hartge M, Sprang C, Frost N . Metabolic actions of estrogen receptor beta (ERbeta) are mediated by a negative cross-talk with PPARgamma. PLoS Genet. 2008; 4(6):e1000108. PMC: 2432036. DOI: 10.1371/journal.pgen.1000108. View

11.

Cai W, Rambaud J, Teboul M, Masse I, Benoit G, Gustafsson J . Expression levels of estrogen receptor beta are modulated by components of the molecular clock. Mol Cell Biol. 2007; 28(2):784-93. PMC: 2223432. DOI: 10.1128/MCB.00233-07. View

12.

Walf A, Rhodes M, Frye C . Antidepressant effects of ERbeta-selective estrogen receptor modulators in the forced swim test. Pharmacol Biochem Behav. 2004; 78(3):523-9. DOI: 10.1016/j.pbb.2004.03.023. View

13.

Kurosawa T, Hiroi H, Tsutsumi O, Ishikawa T, Osuga Y, Fujiwara T . The activity of bisphenol A depends on both the estrogen receptor subtype and the cell type. Endocr J. 2002; 49(4):465-71. DOI: 10.1507/endocrj.49.465. View

14.

Cheng X, Hart G . Alternative O-glycosylation/O-phosphorylation of serine-16 in murine estrogen receptor beta: post-translational regulation of turnover and transactivation activity. J Biol Chem. 2001; 276(13):10570-5. DOI: 10.1074/jbc.M010411200. View

15.

Lampe J . Isoflavonoid and lignan phytoestrogens as dietary biomarkers. J Nutr. 2003; 133 Suppl 3:956S-964S. DOI: 10.1093/jn/133.3.956S. View

16.

Le H, Carlson E, Chua J, Belcher S . Bisphenol A is released from polycarbonate drinking bottles and mimics the neurotoxic actions of estrogen in developing cerebellar neurons. Toxicol Lett. 2007; 176(2):149-56. PMC: 2254523. DOI: 10.1016/j.toxlet.2007.11.001. View

17.

Lang I, Galloway T, Scarlett A, Henley W, Depledge M, Wallace R . Association of urinary bisphenol A concentration with medical disorders and laboratory abnormalities in adults. JAMA. 2008; 300(11):1303-10. DOI: 10.1001/jama.300.11.1303. View

18.

Hughes Z, Liu F, Platt B, Dwyer J, Pulicicchio C, Zhang G . WAY-200070, a selective agonist of estrogen receptor beta as a potential novel anxiolytic/antidepressant agent. Neuropharmacology. 2008; 54(7):1136-42. DOI: 10.1016/j.neuropharm.2008.03.004. View

19.

Hargreaves D, Potten C, Harding C, Shaw L, Morton M, Roberts S . Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab. 1999; 84(11):4017-24. DOI: 10.1210/jcem.84.11.6152. View

20.

Kume K, Zylka M, Sriram S, Shearman L, Weaver D, Jin X . mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell. 1999; 98(2):193-205. DOI: 10.1016/s0092-8674(00)81014-4. View