ArticleHepatology (Baltimore, Md.)2013
Intrahepatic cholestasis of pregnancy levels of sulfated progesterone metabolites inhibit farnesoid X receptor resulting in a cholestatic phenotype.
Article in Hepatology (Baltimore, Md.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 3 of them syntheses that pooled it.
What it found
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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.
The trial behind it
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
79 citing papers in PubMed, 3 syntheses or guidelines pooled it, 182 citations in OpenAlex.
- GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements.Nature communications · 2022Pooled it
- Intrahepatic cholestasis of pregnancy and maternal dyslipidemia: a systematic review and meta-analysis.Acta obstetricia et gynecologica Scandinavica · 2022Pooled it
- Total serum bile acids or serum bile acid profile, or both, for the diagnosis of intrahepatic cholestasis of pregnancy.The Cochrane database of systematic reviews · 2019Pooled it
- Promoter DNA methylation of farnesoid X receptor and pregnane X receptor modulates the intrahepatic cholestasis of pregnancy phenotype.PloS one · 2014Trial
- Molecular Mechanisms of the Gut-Liver-Placenta Axis in Intrahepatic Cholestasis of Pregnancy: Microbiota-Associated Pathogenesis and Next-Generation Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Scratching the Surface: Lipidomic Profiling of the Stratum Corneum in the Search for Pruritogens in Cholestatic Liver Diseases.Journal of personalized medicine · 2026Review
- Ultrasound-derived fat fraction and automated point shear-wave elastography in diagnosing intrahepatic cholestasis of pregnancy and preeclampsia.BMC pregnancy and childbirth · 2026Article
- The evaluation of Xenin-25 levels in intrahepatic cholestasis of pregnancy and comparison with healthy pregnant women.BMC pregnancy and childbirth · 2026Article
- Altered Bile Acid Transport in Liver Disease.Biomedicines · 2026Review
- Liver Conditions Specific to Pregnancy: Optimizing Management and Outcomes.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2026Review
- Application of in vitro to in vivo extrapolation (IVIVE) to inform chemical health guidance value derivation-sample case studies comparing neuro-, hepato-, and developmental toxicities.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Developmental programming: gestational exposure to excess testosterone disrupts maternal steroid homeostasis and perturbs the steroid-lipid relationship in sheep.Molecular and cellular endocrinology · 2026Article
- 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
- Serum steroid metabolome pattern is associated with the response to prednisolone therapy of male patients with IgA nephropathy.Renal failure · 2025Article
- The history and future of bile acid therapies.Journal of hepatology · 2025Article
- Intrahepatic Cholestasis of Pregnancy: Neonatal Impact Through the Lens of Current Evidence.Biomedicines · 2025Review
- A RareJournal of clinical medicine · 2025Article
- Intrahepatic cholestasis of pregnancy.Nature reviews. Disease primers · 2025Review
- Steroids Static Postural Balance Changes After Exercise Intervention Correlate with Steroidome in Elderly Female.Metabolites · 2025Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
unlabelledIntrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy-specific liver disease and is associated with an increased risk of adverse fetal outcomes, including preterm labor and intrauterine death. The endocrine signals that cause cholestasis are not known but 3α-sulfated progesterone metabolites have been shown to be elevated in ICP, leading us to study the impact of sulfated progesterone metabolites on farnesoid X receptor (FXR)-mediated bile acid homeostasis pathways. Here we report that the 3β-sulfated progesterone metabolite epiallopregnanolone sulfate is supraphysiologically raised in the serum of ICP patients. Mice challenged with cholic acid developed hypercholanemia and a hepatic gene expression profile indicative of FXR activation. However, coadministration of epiallopregnanolone sulfate with cholic acid exacerbated the hypercholanemia and resulted in aberrant gene expression profiles for hepatic bile acid-responsive genes consistent with cholestasis. We demonstrate that levels of epiallopregnanolone sulfate found in ICP can function as a partial agonist for FXR, resulting in the aberrant expression of bile acid homeostasis genes in hepatoma cell lines and primary human hepatocytes. Furthermore, epiallopregnanolone sulfate inhibition of FXR results in reduced FXR-mediated bile acid efflux and secreted FGF19. Using cofactor recruitment assays, we show that epiallopregnanolone sulfate competitively inhibits bile acid-mediated recruitment of cofactor motifs to the FXR-ligand binding domain.
conclusionOur results reveal a novel molecular interaction between ICP-associated levels of the 3β-sulfated progesterone metabolite epiallopregnanolone sulfate and FXR that couples the endocrine component of pregnancy in ICP to abnormal bile acid homeostasis.
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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.