ArticleEMBO molecular medicine2014
The uterine and vascular actions of estetrol delineate a distinctive profile of estrogen receptor α modulation, uncoupling nuclear and membrane activation.
Article in EMBO molecular medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 117 citations in OpenAlex.
- Estetrol-Drospirenone combination oral contraceptive: a clinical study of contraceptive efficacy, bleeding pattern and safety in Europe and Russia.BJOG : an international journal of obstetrics and gynaecology · 2022Trial
- A multicenter, randomized study to select the minimum effective dose of estetrol (E4) in postmenopausal women (E4Relief): part 1. Vasomotor symptoms and overall safety.Menopause (New York, N.Y.) · 2020Trial
- Unique effects on hepatic function, lipid metabolism, bone and growth endocrine parameters of estetrol in combined oral contraceptives.The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception · 2015Trial
- Impact of estetrol and drospirenone combination therapy on alleviation of the pelvic pain of endometriosis: a randomized control trial.F&S reports · 2026Article
- Preconditioning and Posttreatment Strategies in Neonatal Hypoxic-Ischemic Encephalopathy: Recent Advances and Clinical Challenges.Molecular neurobiology · 2025Review
- Role of Membrane Estrogen Receptor Alpha on the Positive Feedback of Estrogens on Kisspeptin and GnRH Neurons.eNeuro · 2024Article
- Estetrol Inhibits Endometriosis Development in an In Vivo Murine Model.Biomolecules · 2024Article
- Estetrol/GPER/SERPINB2 transduction signaling inhibits the motility of triple-negative breast cancer cells.Journal of translational medicine · 2024Article
- Interrogating Estrogen Signaling Pathways in Human ER-Positive Breast Cancer Cells Forming Bone Metastases in Mice.Endocrinology · 2024Article
- Reversible female contraceptives: historical, current, and future perspectives†.Biology of reproduction · 2024Review
- Reprogramming of endothelial gene expression by tamoxifen inhibits angiogenesis and ERα-negative tumor growth.Theranostics · 2024Article
- Review
- Peering into the Brain's Estrogen Receptors: PET Tracers for Visualization of Nuclear and Extranuclear Estrogen Receptors in Brain Disorders.Biomolecules · 2023Article
- Comparison of Estetrol Exposure between Women and Mice to Model Preclinical Experiments and Anticipate Human Treatment.International journal of molecular sciences · 2023Article
- Estetrol: From Preclinical to Clinical Pharmacology and Advances in the Understanding of the Molecular Mechanism of Action.Drugs in R&D · 2023Review
- Estetrol Increases Progesterone Genetic Response without Triggering Common Estrogenic Effects in Endometriotic Cell Lines and Primary Cultures.Biomedicines · 2023Article
- The different natural estrogens promote endothelial healing through distinct cell targets.JCI insight · 2023Article
- The emerging role of estrogen's non-nuclear signaling in the cardiovascular disease.Frontiers in cardiovascular medicine · 2023Review
- Low Thrombin Generation in Users of a Contraceptive Containing Estetrol and Drospirenone.The Journal of clinical endocrinology and metabolism · 2022Article
- Membrane-Initiated Estrogen, Androgen, and Progesterone Receptor Signaling in Health and Disease.Endocrine reviews · 2022Review
Corrections and comments
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Authors and funding
29 authors at 8 institutions in 3 countries.
Funding
Abstract
Estetrol (E4) is a natural estrogen with a long half-life produced only by the human fetal liver during pregnancy. The crystal structures of the estrogen receptor α (ERα) ligand-binding domain bound to 17β-estradiol (E2) and E4 are very similar, as well as their capacity to activate the two activation functions AF-1 and AF-2 and to recruit the coactivator SRC3. In vivo administration of high doses of E4 stimulated uterine gene expression, epithelial proliferation, and prevented atheroma, three recognized nuclear ERα actions. However, E4 failed to promote endothelial NO synthase activation and acceleration of endothelial healing, two processes clearly dependent on membrane-initiated steroid signaling (MISS). Furthermore, E4 antagonized E2 MISS-dependent effects in endothelium but also in MCF-7 breast cancer cell line. This profile of ERα activation by E4, uncoupling nuclear and membrane activation, characterizes E4 as a selective ER modulator which could have medical applications that should now be considered further.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.