ArticleProceedings of the National Academy of Sciences of the United States of America2010
Gonadotropin-positive pituitary tumors accompanied by ovarian tumors in aging female ERbeta-/- mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- The Role of Estrogen Signaling Pathway and Targeted Therapy Exploration in Urological Tumors.International journal of biological sciences · 2026Review
- A Dynamic Shift in Estrogen Receptor Expression During Granulosa Cell Differentiation in the Ovary.Endocrinology · 2025Article
- ERβ in Granulosa Cell Tumors and Its Clinical Potential.Endocrinology · 2023Review
- A Phosphotyrosine Switch in Estrogen Receptor β Is Required for Mouse Ovarian Function.Frontiers in cell and developmental biology · 2021Article
- Characterizing Endocrine Status, Tumor Hypoxia and Immunogenicity for Therapy Success in Epithelial Ovarian Cancer.Frontiers in endocrinology · 2021Review
- FSH Levels Are Related to E-cadherin Expression and Subcellular Location in Nonfunctioning Pituitary Tumors.The Journal of clinical endocrinology and metabolism · 2020Article
- Ventral prostate and mammary gland phenotype in mice with complete deletion of the ERβ gene.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Constitutive Activation of PI3K in Oocyte Induces Ovarian Granulosa Cell Tumors.Cancer research · 2016Article
- Insights into granulosa cell tumors using spontaneous or genetically engineered mouse models.Clinical and experimental reproductive medicine · 2016Review
- Role of estrogen receptor α and β in preserving hippocampal function during aging.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2013Article
- Minireview: animal models and mechanisms of ovarian cancer development.Endocrinology · 2012Review
- The putative G-protein coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian and breast cancer cells in a GPER-independent manner.American journal of translational research · 2012Article
- The different roles of ER subtypes in cancer biology and therapy.Nature reviews. Cancer · 2011Review
- Pathogenesis of pituitary tumors.Nature reviews. Endocrinology · 2011Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
At 2 years of age, 100% (23/23) of ERbeta(-/-) female mice have developed large pituitary and ovarian tumors. The pituitary tumors are gonadotropin-positive and the ovarian tumors are sex cord (less differentiated) and granulosa cell tumors (differentiated and estrogen secreting). No male mice had pituitary tumors and no pituitary or ovarian tumors developed in ERalpha(-/-) mice or in ERalphabeta(-/-) double knockout mice. The tumors have high proliferation indices, are ERalpha-positive, ERbeta-negative, and express high levels of nuclear phospho-SMAD3. Mice with granulosa cell tumors also had hyperproliferative endometria. The cause of the pituitary tumors appeared to be excessive secretion of gonadotropin releasing hormone (GnRH) from the hypothalamus resulting from high expression of NPY. The ovarian phenotype is similar to that seen in mice where inhibin is ablated. The data indicate that ERbeta plays an important role in regulating GnRH secretion. We suggest that in the absence of ERbeta, the proliferative action of FSH/SMAD3 is unopposed and the high proliferation leads to the development of ovarian tumors. The absence of tumors in the ERalphabeta(-/-) mice suggests that tumor development requires the presence of ERalpha.
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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.