ArticleGastroenterology2012
Estrogen receptor α represses transcription of HBV genes via interaction with hepatocyte nuclear factor 4α.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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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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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 133 citations in OpenAlex.
- Intricate roles of estrogen and estrogen receptors in digestive system cancers: a systematic review.Cancer biology & medicine · 2024Pooled it
- Sex differences in non-reproductive cancers: mechanistic roles of sex-hormone signaling.Cell communication and signaling : CCS · 2026Review
- Sex differences in immune responses to viruses, bacteria and vaccines.Nature immunology · 2026Review
- IFI35 suppresses the transcription of hepatitis B virus cccDNA minichromosome via promoting HNF4α proteasomal degradation.Journal of biomedical science · 2026Article
- Impact of donor-recipient sex-matching patterns on liver transplantation outcomes: a cohort study based on United Network of Organ Sharing data.Hepatobiliary surgery and nutrition · 2025Article
- Identification of glycogen synthase kinase 3alpha/beta as a host factor required for HBV transcription using high-throughput screening.Hepatology (Baltimore, Md.) · 2025Article
- Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity.Clinical and molecular hepatology · 2025Article
- Sequential activation of ERα-AMPKα signaling by the flavonoid baicalin down-regulates viral HNF-dependent HBV replication.Acta pharmacologica Sinica · 2025Article
- Estrogen and viral infection.Frontiers in immunology · 2025Review
- Combined therapy with the estrogen receptor ERα and IFNα-2b suppresses HBV replication by inducing GBP1 expression.Frontiers in immunology · 2025Article
- Targeting HBV cccDNA Levels: Key to Achieving Complete Cure of Chronic Hepatitis B.Pathogens (Basel, Switzerland) · 2024Review
- Tripartite Motif-Containing Protein 65 (TRIM65) Inhibits Hepatitis B Virus Transcription.Viruses · 2024Article
- Patients with chronic hepatitis B who have persistently normal alanine aminotransferase or aged < 30 years may exhibit significant histologic damage.BMC gastroenterology · 2024Article
- Gender-specific alteration of steroid metabolism and its impact on viral replication in a mouse model of hepatitis B virus infection.Animal cells and systems · 2024Article
- Maternal Exercise Prior to and during Gestation Induces Sex-Specific Alterations in the Mouse Placenta.International journal of molecular sciences · 2023Article
- Hyperpolarization-activated cyclic nucleotide-gated cation channel 3 promotes HCC development in a female-biased manner.Cell reports · 2023Article
- Two genetic variants in the SRD5A2 gene are found to be associated with sex differences in the disease characteristics of patients with chronic hepatitis B virus infection.Biology of sex differences · 2023Article
- Review
- Antibiotic-induced gut bacteria depletion has no effect on HBV replication in HBV immune tolerance mouse model.Virologica Sinica · 2023Article
- Many Ways to Communicate-Crosstalk between the HBV-Infected Cell and Its Environment.Pathogens (Basel, Switzerland) · 2022Review
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsWomen with hepatitis B virus (HBV) infection usually have lower viral loads than men, reducing their risk of liver cancer. There are 2 androgen-responsive elements in the HBV enhancer I that contribute to higher viral titers in men. We investigated whether and how estrogen signaling affects progression of HBV infection.
methodsOvariectomy and estrogen supplementation were used to evaluate the effect of estrogen on HBV titers in transgenic mice with replicating HBV in hepatocytes. The effect of estrogen signaling on transcription of HBV genes, and the mechanisms of regulation, were studied in HepG2 cells.
resultsHBV titers increased in female mice after ovariectomy and decreased in male mice supplemented with estrogen. Hepatic expression of estrogen receptor (ER)-α was increased by estrogen exposure. In HepG2 cells, up-regulation of ER-α reduced HBV transcription, which required a specific region within enhancer I. Direct DNA binding of ER-α and histone deacetylase activity were not required for ER-α-mediated repression of HBV genes. Overexpression of hepatocyte nuclear factor (HNF)-4α, which binds to this region, overcame the repressive effect of ER-α. ER-α did not repress transcription of an HBV replicon with a mutant HNF-4α binding site within enhancer I. Coimmunoprecipitation assays showed an interaction between ER-α and HNF-4α; this interaction prevented HNF-4α binding to enhancer I and activation of HBV transcription.
conclusionsEstrogen can repress transcription of HBV genes by up-regulating ER-α, which interacts with and alters binding of HNF-4α to the HBV enhancer I. These findings might account for the lower viral load and reduced incidence of liver cancer in HBV-infected women than men.
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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.