Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical Implications
- PMID: 28539435
- DOI: 10.1152/physrev.00024.2016
Membrane and Nuclear Estrogen Receptor Alpha Actions: From Tissue Specificity to Medical Implications
Abstract
Estrogen receptor alpha (ERα) has been recognized now for several decades as playing a key role in reproduction and exerting functions in numerous nonreproductive tissues. In this review, we attempt to summarize the in vitro studies that are the basis of our current understanding of the mechanisms of action of ERα as a nuclear receptor and the key roles played by its two activation functions (AFs) in its transcriptional activities. We then depict the consequences of the selective inactivation of these AFs in mouse models, focusing on the prominent roles played by ERα in the reproductive tract and in the vascular system. Evidence has accumulated over the two last decades that ERα is also associated with the plasma membrane and activates non-nuclear signaling from this site. These rapid/nongenomic/membrane-initiated steroid signals (MISS) have been characterized in a variety of cell lines, and in particular in endothelial cells. The development of selective pharmacological tools that specifically activate MISS and the generation of mice expressing an ERα protein impeded for membrane localization have begun to unravel the physiological role of MISS in vivo. Finally, we discuss novel perspectives for the design of tissue-selective ER modulators based on the integration of the physiological and pathophysiological roles of MISS actions of estrogens.
Copyright © 2017 the American Physiological Society.
Similar articles
-
Segregation of nuclear and membrane-initiated actions of estrogen receptor using genetically modified animals and pharmacological tools.Mol Cell Endocrinol. 2022 Jan 1;539:111467. doi: 10.1016/j.mce.2021.111467. Epub 2021 Oct 7. Mol Cell Endocrinol. 2022. PMID: 34626731 Review.
-
Predominant Role of Nuclear Versus Membrane Estrogen Receptor α in Arterial Protection: Implications for Estrogen Receptor α Modulation in Cardiovascular Prevention/Safety.J Am Heart Assoc. 2018 Jun 29;7(13):e008950. doi: 10.1161/JAHA.118.008950. J Am Heart Assoc. 2018. PMID: 29959137 Free PMC article.
-
Estrogen receptor subcellular localization and cardiometabolism.Mol Metab. 2018 Sep;15:56-69. doi: 10.1016/j.molmet.2018.05.009. Epub 2018 May 16. Mol Metab. 2018. PMID: 29807870 Free PMC article. Review.
-
Nuclear and Membrane Actions of Estrogen Receptor Alpha: Contribution to the Regulation of Energy and Glucose Homeostasis.Adv Exp Med Biol. 2017;1043:401-426. doi: 10.1007/978-3-319-70178-3_19. Adv Exp Med Biol. 2017. PMID: 29224105 Review.
-
Mutation of the palmitoylation site of estrogen receptor α in vivo reveals tissue-specific roles for membrane versus nuclear actions.Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):E283-90. doi: 10.1073/pnas.1322057111. Epub 2013 Dec 26. Proc Natl Acad Sci U S A. 2014. PMID: 24371309 Free PMC article.
Cited by
-
Identification of modules and key genes associated with breast cancer subtypes through network analysis.Sci Rep. 2024 May 29;14(1):12350. doi: 10.1038/s41598-024-61908-4. Sci Rep. 2024. PMID: 38811600 Free PMC article.
-
Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.Life (Basel). 2024 Apr 30;14(5):582. doi: 10.3390/life14050582. Life (Basel). 2024. PMID: 38792602 Free PMC article. Review.
-
Interrogating Estrogen Signaling Pathways in Human ER-Positive Breast Cancer Cells Forming Bone Metastases in Mice.Endocrinology. 2024 Apr 29;165(6):bqae038. doi: 10.1210/endocr/bqae038. Endocrinology. 2024. PMID: 38715255
-
Androgen receptor and estrogen receptor variants in prostate and breast cancers.J Steroid Biochem Mol Biol. 2024 Jul;241:106522. doi: 10.1016/j.jsbmb.2024.106522. Epub 2024 Apr 17. J Steroid Biochem Mol Biol. 2024. PMID: 38641298 Review.
-
Reprogramming of endothelial gene expression by tamoxifen inhibits angiogenesis and ERα-negative tumor growth.Theranostics. 2024 Jan 1;14(1):249-264. doi: 10.7150/thno.87306. eCollection 2024. Theranostics. 2024. PMID: 38164151 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources