ArticleProceedings of the National Academy of Sciences of the United States of America2014
The estrogen receptor antagonist ICI 182,780 can act both as an agonist and an inverse agonist when estrogen receptor α AF-2 is modified.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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.
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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.
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Who cites it
30 citing papers in PubMed, 55 citations in OpenAlex.
- Estrogen-like potentiation of ghrelin-stimulated GH secretion by fulvestrant, a putatively selective ER antagonist, in postmenopausal women.The Journal of clinical endocrinology and metabolism · 2014Trial
- Stomach at the crossroads: nuclear receptor signaling at the interface between what we are and what we eat.Physiological reviews · 2026Review
- Bibliometric Analysis of The Global Research Trends on The Application of Tamoxifen in The Treatment of Breast Cancer Over The Past 50 Years.The Malaysian journal of medical sciences : MJMS · 2025Review
- Article
- TNFR1/p38αMAPK signaling in Nex + supraspinal neurons regulates estrogen-dependent chronic neuropathic pain.Brain, behavior, and immunity · 2024Article
- Oestrogen receptor positive breast cancer and its embedded mechanism: breast cancer resistance to conventional drugs and related therapies, a review.Open biology · 2024Review
- Review
- Exploring the Potential of Lapatinib, Fulvestrant, and Paclitaxel Conjugated with Glycidylated PAMAM G4 Dendrimers for Cancer and Parasite Treatment.Molecules (Basel, Switzerland) · 2023Article
- The race to develop oral SERDs and other novel estrogen receptor inhibitors: recent clinical trial results and impact on treatment options.Cancer metastasis reviews · 2022Review
- Andrographolide Exhibits Anticancer Activity against Breast Cancer Cells (MCF-7 and MDA-MB-231 Cells) through Suppressing Cell Proliferation and Inducing Cell Apoptosis via Inactivation of ER-α Receptor and PI3K/AKT/mTOR Signaling.Molecules (Basel, Switzerland) · 2022Article
- The physiological role of estrogen receptor functional domains.Essays in biochemistry · 2021Review
- Estrogen Receptors as Molecular Targets of Endocrine Therapy for Glioblastoma.International journal of molecular sciences · 2021Review
- Schisandrol A Exhibits Estrogenic Activity via Estrogen Receptor α-Dependent Signaling Pathway in Estrogen Receptor-Positive Breast Cancer Cells.Pharmaceutics · 2021Article
- Sex-specific responses in trabecular and cortical microstructure of tibia due to repeated irradiation from micro-computed tomography in adult CD-1 mice.Bone reports · 2020Article
- Endocrine resistant breast cancer cells with loss of ERα expression retain proliferative ability by reducing caspase7-mediated HDAC3 cleavage.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Construction of reporter gene assays usingGenes and environment : the official journal of the Japanese Environmental Mutagen Society · 2020Article
- Transactivation Function-1-Mediated Partial Agonist Activity of Selective Estrogen Receptor Modulator Requires Homo-Dimerization of the Estrogen Receptor α Ligand Binding Domain.International journal of molecular sciences · 2019Review
- Effects of Bisphenol A and 4-tert-Octylphenol on Embryo Implantation Failure in Mouse.International journal of environmental research and public health · 2018Article
- Estrogens and Androgens in Skeletal Physiology and Pathophysiology.Physiological reviews · 2017Review
- A Review of Fulvestrant in Breast Cancer.Oncology and therapy · 2017Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bone-sparing effect of estrogen is primarily mediated via estrogen receptor (ER) α, which stimulates target gene transcription through two activation functions (AFs), AF-1 in the N-terminal and AF-2 in the ligand-binding domain. It was recently demonstrated that the ER antagonist ICI 182,780 (ICI) acts as an ER agonist in uterus of mice with mutations in the ERα AF-2. To evaluate the estrogen-like effects of ICI in different tissues, ovariectomized wild-type mice and mice with mutations in the ERα AF-2 (ERαAF-2(0)) were treated with ICI, estradiol, or vehicle for 3 wk. Estradiol increased the trabecular and cortical bone mass as well as the uterine weight, whereas it reduced fat mass, thymus weight, and the growth plate height in wild-type but not in ERαAF-2(0) mice. Although ICI had no effect in wild-type mice, it exerted tissue-specific effects in ERαAF-2(0) mice. It acted as an ERα agonist on trabecular bone mass and uterine weight, whereas no effect was seen on cortical bone mass, fat mass, or thymus weight. Surprisingly, a pronounced inverse agonistic activity was seen on the growth plate height, resulting in enhanced longitudinal bone growth. In conclusion, ICI uses ERα AF-1 in a tissue-dependent manner in mice lacking ERαAF-2, resulting in no effect, agonistic activity, or inverse agonistic activity. We propose that ERα lacking AF-2 is constitutively active in the absence of ligand in the growth plate, enabling ICI to act as an inverse agonist.
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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.