Transcriptional activity of estrogen-related receptor γ (ERRγ) is stimulated by the phytoestrogen equol
Abstract
Estrogen-related receptor γ (ERRγ) is an orphan nuclear receptor lacking identified natural ligands. The synthetic estrogen receptor ligands 4-hydroxytamoxifen and diethylstilbestrol have, however, been shown to bind to and abolish the constitutive transcriptional activity of ERRγ. Certain phytoestrogens were recently reported to act as agonists of the related ERRα. We investigated whether phytoestrogens also modulated the transcriptional activity of ERRγ. We analyzed a selection of phytoestrogens for their potential agonistic or antagonistic activity on ERRγ. In transiently transfected PC-3 and U2-OS cells equol stimulated the transcriptional activity of ERRγ and enhanced its interaction with the coactivator GRIP1. The agonistic effect of equol was abolished by 4-hydroxytamoxifen. Equol induced a conformational change in the ERRγ ligand-binding domain. Based on structural models of the ERRγ ligand-binding domain, we were able to introduce mutations that modulated the agonistic potential of equol. Finally, equol enhanced the growth inhibitory effect of ERRγ on the prostate cancer PC-3 cells. In conclusion, we have demonstrated that the phytoestrogen equol acts as an ERRγ agonist.
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Equol may enhance the skin's barrier function and cellular integrity via its topical application and sustained delivery mechanism.
“Undoubtedly, equol may enhance the skin's barrier function and cellular integrity via its topical application and sustained delivery mechanism [12,82].”
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Skin aging and oxidative stress: Equol’s anti-aging effects via biochemical and molecular mechanisms
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- Authors
- Hirvonen, J., Rajalin, A.-M., Wohlfahrt, G., Adlercreutz, H., Wähälä, K., & Aarnisalo, P.
- Affiliations
- University of Helsinki (FI)
- Orion Corporation (Finland) (FI)
- Corresponding author
- Aarnisalo, Piia
- Venue
- The Journal of Steroid Biochemistry and Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 123
- Issue
- 1-2
- Pages
- 46-57
- ISSN
- 0960-0760 (ISSN-L)
- OpenAlex
- W1969254924
- Cited by
- 35
- References
- 61
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 4 · 2015: 5 · 2014: 1 · 2013: 8 · 2012: 2
- FWCI
- 2.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- Päivikki ja Sakari Sohlbergin Säätiö
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Keywords
- estrogen-related receptor gamma, equol, phytoestrogens, orphan nuclear receptor, transcriptional activation, 4-hydroxytamoxifen, prostate cancer, PC-3 cells, estrogen receptor agonists
- MeSH terms
- ERRalpha Estrogen-Related Receptor, Animals, Estrogen Antagonists, Humans, Isoflavones, Receptors, Estrogen, Transcriptional Activation, Cell Line, Tumor, Phytoestrogens, Mice, Equol
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