ArticleMolecular endocrinology (Baltimore, Md.)2008
Liver receptor homolog-1 regulates bile acid homeostasis but is not essential for feedback regulation of bile acid synthesis.
Article in Molecular endocrinology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 153 citations in OpenAlex.
- From hepatic to hematopoietic: LRH-1's expanding cellular repertoire to the immune system.The FEBS journal · 2026Review
- Nitroxoline mitigates hepatic steatosis by enhancing cholesterol efflux and promoting bile acid synthesis through LRH-1 signaling.Lipids in health and disease · 2025Article
- Differential Expression Characteristics of Two IsoformsAnimals : an open access journal from MDPI · 2025Article
- The self-renewal function of Oct-4 can be replaced by the EWS-Oct-4 fusion protein in embryonic stem cells.Cellular and molecular life sciences : CMLS · 2025Article
- Fragment-Based Discovery of Drug-like LRH-1 Agonists.ACS medicinal chemistry letters · 2025Article
- Fatty Acid Mimetic Fragments as Liver Receptor Homologue-1 Modulators.ACS pharmacology & translational science · 2025Article
- Role of Protein Regulators of Cholesterol Homeostasis in Immune Modulation and Cancer Pathophysiology.Endocrinology · 2025Review
- Foxa deficiency restricts hepatitis B virus biosynthesis through epigenic silencing.Journal of virology · 2024Article
- Nuclear receptor 5A2 regulation of Agrp underlies olanzapine-induced hyperphagia.Molecular psychiatry · 2023Review
- Key transcriptional effectors of the pancreatic acinar phenotype and oncogenic transformation.PloS one · 2023Article
- LRH-1/NR5A2 interacts with the glucocorticoid receptor to regulate glucocorticoid resistance.EMBO reports · 2022Article
- The gut-liver axis in cholangiopathies: focus on bile acid based pharmacological treatment.Current opinion in gastroenterology · 2022Review
- Nuclear receptor subfamily 5 group A member 2 (NR5A2): role in health and diseases.Molecular biology reports · 2021Review
- Deletion of Intestinal SHP Impairs Short-term Response to Cholic Acid Challenge in Male Mice.Endocrinology · 2021Article
- Revisiting steroidogenesis and its role in immune regulation with the advanced tools and technologies.Genes and immunity · 2021Review
- Pharmacological LRH-1/Nr5a2 inhibition limits pro-inflammatory cytokine production in macrophages and associated experimental hepatitis.Cell death & disease · 2020Article
- Enhanced GIP Secretion in Obesity Is Associated with Biochemical Alteration and miRNA Contribution to the Development of Liver Steatosis.Nutrients · 2020Article
- The Protective Effects of Imperatorin on Acetaminophen Overdose-Induced Acute Liver Injury.Oxidative medicine and cellular longevity · 2020Article
- Intestinal Absorption of Bile Acids in Health and Disease.Comprehensive Physiology · 2019Review
- Article
20 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Liver receptor homolog 1 (LRH-1), an orphan nuclear receptor, is highly expressed in liver and intestine, where it is implicated in the regulation of cholesterol, bile acid, and steroid hormone homeostasis. Among the proposed LRH-1 target genes in liver are those encoding cholesterol 7alpha-hydroxylase (CYP7A1) and sterol 12alpha-hydroxylase (CYP8B1), which catalyze key steps in bile acid synthesis. In vitro studies suggest that LRH-1 may be involved both in stimulating basal CYP7A1 and CYP8B1 transcription and in repressing their expression as part of the nuclear bile acid receptor [farnesoid X receptor (FXR)]-small heterodimer partner signaling cascade, which culminates in small heterodimer partner binding to LRH-1 to repress gene transcription. However, in vivo analysis of LRH-1 actions has been hampered by the embryonic lethality of Lrh-1 knockout mice. To overcome this obstacle, mice were generated in which Lrh-1 was selectively disrupted in either hepatocytes or intestinal epithelium. LRH-1 deficiency in either tissue changed mRNA levels of genes involved in cholesterol and bile acid homeostasis. Surprisingly, LRH-1 deficiency in hepatocytes had no significant effect on basal Cyp7a1 expression or its repression by FXR. Whereas Cyp8b1 repression by FXR was also intact in mice deficient for LRH-1 in hepatocytes, basal CYP8B1 mRNA levels were significantly decreased, and there were corresponding changes in the composition of the bile acid pool. Taken together, these data reveal a broad role for LRH-1 in regulating bile acid homeostasis but demonstrate that LRH-1 is either not involved in the feedback regulation of bile acid synthesis or is compensated for by other factors.
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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.