ArticleGastroenterology2019
Estrogen Activation of G-Protein-Coupled Estrogen Receptor 1 Regulates Phosphoinositide 3-Kinase and mTOR Signaling to Promote Liver Growth in Zebrafish and Proliferation of Human Hepatocytes.
Article in Gastroenterology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Association between blood lipid levels and the risk of liver cancer: a systematic review and meta-analysis.Cancer causes & control : CCC · 2024Pooled it
- Unveiling the role of aldosterone in metabolic dysfunction-associated steatotic liver disease.Reviews in endocrine & metabolic disorders · 2026Review
- Sexual dimorphism in the liver.Nature reviews. Gastroenterology & hepatology · 2026Review
- Identification of the CYP19A1-GPER1 axis as a critical oncogenic driver in hepatocellular carcinoma via AKT activation.Journal of translational medicine · 2026Article
- EREG-secreting THBS1Hepatobiliary surgery and nutrition · 2026Article
- The relationship between metabolic associated fatty liver disease and thyroid nodule: a cross-sectional study in China.BMC gastroenterology · 2026Observational
- Comprehensive genomic profiling of triple-negative breast cancer metastases identifies role of PKD1 in immunotherapy resistance.The Journal of clinical investigation · 2026Article
- Human Cancers Derived from Either Genetic or Lifestyle Factors Are Initiated by Impaired Estrogen Signaling.Cancers · 2025Review
- The Impact of Estrogen Deficiency on Liver Metabolism: Implications for Hormone Replacement Therapy.Endocrine reviews · 2025Review
- A Systematic Review of Estrogens as Emerging Contaminants in Water: A Global Overview Study from the One Health Perspective.Journal of xenobiotics · 2025Review
- Analysis of the factors influencing liver regeneration after hepatectomy in hepatocellular carcinoma patients and the relationship between liver regeneration and prognosis.Scientific reports · 2025Article
- High Temperature and Ethinylestradiol May Reduce Body Growth, Liver and Hepatocyte Volumes and Lipid Droplets in Adult Male Guppies.Animals : an open access journal from MDPI · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- Sex reversal induced by 17β-estradiol may be achieved by regulating the neuroendocrine system of the Pacific white shrimp Penaeus vannamei.BMC genomics · 2025Article
- Asparagine synthetase and G-protein coupled estrogen receptor are critical responders to nutrient supply in KRAS mutant colorectal cancer.International journal of cancer · 2025Article
- Hydrogel-Based Strategies for Liver Tissue Engineering.Chem & bio engineering · 2024Review
- Steroid hormones in fish, caution for present and future: A review.Toxicology reports · 2024Review
- Adhesive lipophilic gels delivering rapamycin prevent oral leukoplakia from malignant transformation.Materials today. Bio · 2024Article
- Hormone-induced thrombosis is mediated through non-canonical fibrin(ogen) aggregation and a novel estrogen target in zebrafish.bioRxiv : the preprint server for biology · 2024Article
- Sex hormone receptors, calcium-binding protein and Yap1 signaling regulate sex-dependent liver cell proliferation following partial hepatectomy.Disease models & mechanisms · 2024Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsPatients with cirrhosis are at high risk for hepatocellular carcinoma (HCC) and often have increased serum levels of estrogen. It is not clear how estrogen promotes hepatic growth. We investigated the effects of estrogen on hepatocyte proliferation during zebrafish development, liver regeneration, and carcinogenesis. We also studied human hepatocytes and liver tissues.
methodsZebrafish were exposed to selective modifiers of estrogen signaling at larval and adult stages. Liver growth was assessed by gene expression, fluorescent imaging, and histologic analyses. We monitored liver regeneration after hepatocyte ablation and HCC development after administration of chemical carcinogens (dimethylbenzanthrazene). Proliferation of human hepatocytes was measured in a coculture system. We measured levels of G-protein-coupled estrogen receptor (GPER1) in HCC and nontumor liver tissues from 68 patients by immunohistochemistry.
resultsExposure to 17β-estradiol (E2) increased proliferation of hepatocytes and liver volume and mass in larval and adult zebrafish. Chemical genetic and epistasis experiments showed that GPER1 mediates the effects of E2 via the phosphoinositide 3-kinase-protein kinase B-mechanistic target of rapamycin pathway: gper1-knockout and mtor-knockout zebrafish did not increase liver growth in response to E2. HCC samples from patients had increased levels of GPER1 compared with nontumor tissue samples; estrogen promoted proliferation of human primary hepatocytes. Estrogen accelerated hepatocarcinogenesis specifically in male zebrafish. Chemical inhibition or genetic loss of GPER1 significantly reduced tumor development in the zebrafish.
conclusionsIn an analysis of zebrafish and human liver cells and tissues, we found GPER1 to be a hepatic estrogen sensor that regulates liver growth during development, regeneration, and tumorigenesis. Inhibitors of GPER1 might be developed for liver cancer prevention or treatment. TRANSCRIPT PROFILING: The accession number in the Gene Expression Omnibus is GSE92544.
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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.