ArticleMolecular endocrinology (Baltimore, Md.)2015
Estrogen and Estrogen Receptor-α-Mediated Transrepression of Bile Salt Export Pump.
Article in Molecular endocrinology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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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Who cites it
20 citing papers in PubMed, 44 citations in OpenAlex.
- Beyond the Pump: The Evolving Molecular Landscape of Intrahepatic Cholestasis.Diagnostics (Basel, Switzerland) · 2026Review
- Cholestatic and autoimmune liver diseases, bile duct injury, oxidative stress, and therapeutic strategies.Frontiers in physiology · 2026Review
- Transcriptional regulation of ubiquitin specific peptidase 2b by farnesoid X receptor and its implications in the pathogenesis of hepatocellular carcinoma.American journal of cancer research · 2026Article
- The history and future of bile acid therapies.Journal of hepatology · 2025Article
- Intrahepatic cholestasis of pregnancy.Nature reviews. Disease primers · 2025Review
- A study on the relationship between gut microbiota and intrahepatic cholestasis of pregnancy.Heliyon · 2024Article
- Sex-Dependent Differences in Cholestasis: Why Estrogen Signaling May Be a Key Pathophysiological Driver.The American journal of pathology · 2023Review
- The Pathological Effects of Circulating Hydrophobic Bile Acids in Alzheimer's Disease.Journal of Alzheimer's disease reports · 2023Review
- Maternal and Fetal Bile Acid Homeostasis Regulated by Sulfated Progesterone Metabolites through FXR Signaling Pathway in a Pregnant Sow Model.International journal of molecular sciences · 2022Article
- Circulatory Metabolomics Reveals the Association of the Metabolites With Clinical Features in the Patients With Intrahepatic Cholestasis of Pregnancy.Frontiers in physiology · 2022Article
- Development of an adverse outcome pathway for intrahepatic cholestasis of pregnancy.Current research in toxicology · 2022Article
- Nuclear Receptors in Pregnancy and Outcomes: Clinical Perspective.Advances in experimental medicine and biology · 2022Article
- The Pathological Mechanisms of Estrogen-Induced Cholestasis: Current Perspectives.Frontiers in pharmacology · 2021Review
- Molecular Pathogenesis of Intrahepatic Cholestasis of Pregnancy.Canadian journal of gastroenterology & hepatology · 2021Review
- Metformin Disrupts Bile Acid Efflux by Repressing Bile Salt Export Pump Expression.Pharmaceutical research · 2020Article
- Mechanistic insights into geniposide regulation of bile salt export pump (BSEP) expression.RSC advances · 2018Article
- Effect of Liver Disease on Hepatic Transporter Expression and Function.Journal of pharmaceutical sciences · 2017Review
- Differential Feedback Regulation of Δ4-3-Oxosteroid 5β-Reductase Expression by Bile Acids.PloS one · 2017Article
- Immunology of hepatic diseases during pregnancy.Seminars in immunopathology · 2016Review
- Immunological basis in the pathogenesis of intrahepatic cholestasis of pregnancy.Expert review of clinical immunology · 2016Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Among diseases unique to pregnancy, intrahepatic cholestasis of pregnancy is the most prevalent disorder with elevated serum bile acid levels. We have previously shown that estrogen 17β-estradiol (E2) transrepresses bile salt export pump (BSEP) through an interaction between estrogen receptor (ER)-α and farnesoid X receptor (FXR) and transrepression of BSEP by E2/ERα is an etiological contributing factor to intrahepatic cholestasis of pregnancy. Currently the mechanistic insights into such transrepression are not fully understood. In this study, the dynamics of coregulator recruitment to BSEP promoter after FXR activation and E2 treatment were established with quantitative chromatin immunoprecipitation assays. Coactivator peroxisome proliferator-activated receptor-γ coactivator-1 was predominantly recruited to the BSEP promoter upon FXR activation, and its recruitment was decreased by E2 treatment. Meanwhile, recruitment of nuclear receptor corepressor was markedly increased upon E2 treatment. Functional evaluation of ERα and ERβ chimeras revealed that domains AC of ERα are the determinants for ERα-specific transrepression on BSEP. Further studies with various truncated ERα proteins identified the domains in ERα responsible for ligand-dependent and ligand-independent transrepression. Truncated ERα-AD exhibited potent ligand-independent transrepressive activity, whereas ERα-CF was fully capable of transrepressing BSEP ligand dependently in vitro in Huh 7 cells and in vivo in mice. Both ERα-AD and ERα-CF proteins were associated with FXR in the coimmunoprecipitation assays. In conclusion, E2 repressed BSEP expression through diminishing peroxisome proliferator-activated receptor-γ coactivator-1 recruitment with a concurrent increase in nuclear receptor corepressor recruitment to the BSEP promoter. Domains AD and CF in ERα mediated ligand-independent and ligand-dependent transrepression on BSEP, respectively, through interacting with FXR.
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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.