{"doi":"10.1210/me.2007-0565","title":"Liver Receptor Homolog-1 Regulates Bile Acid Homeostasis but Is Not Essential for Feedback Regulation of Bile Acid Synthesis","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>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 7α-hydroxylase (CYP7A1) and sterol 12α-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.</jats:p>","journal":"Molecular Endocrinology","year":2008,"id":603011,"datarank":0.7574784010874307,"base_score":5.049856007249537,"endowment":5.049856007249537,"self_citation_contribution":0.7574784010874307,"citation_network_contribution":0.0,"self_endowment_contribution":0.7574784010874307,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":155,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":405755,"name":"Daniel R. 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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.</jats:p>","is_dataset_classified":null,"base_score":5.049856007249537,"endowment":5.049856007249537,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"18323469","pmcid":"PMC2409274","openalex_id":"https://openalex.org/W1979510879","authors":[],"funders":[{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK067158","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"DK067158","title":null},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null},{"funder_name":"Howard Hughes Medical Institute","grant_id":"","title":null}],"total_grants":4,"fwci":7.5962,"citation_percentile":0.98053797,"influential_citations":0,"citation_trend":[{"year":2012,"count":9},{"year":2013,"count":12},{"year":2014,"count":9},{"year":2015,"count":10},{"year":2016,"count":4},{"year":2017,"count":3},{"year":2018,"count":7},{"year":2019,"count":5},{"year":2020,"count":10},{"year":2021,"count":8},{"year":2022,"count":7},{"year":2023,"count":3},{"year":2024,"count":5},{"year":2025,"count":7},{"year":2026,"count":2}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://academic.oup.com/mend/article-pdf/22/6/1345/8939412/mend1345.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1210/me.2007-0565","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/18323469","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2409274","host_type":"repository"}],"fields_of_study":["Drug Transport and Resistance Mechanisms","Cholesterol and Lipid Metabolism","Pharmacogenetics and Drug Metabolism","Animals","Bile Acids and Salts","Cells, Cultured","Cloning, Molecular","DNA-Binding Proteins","Feedback, Physiological","Hepatocytes","Homeostasis","Intestinal Mucosa","Mice","Mice, Knockout","Organ Specificity","Receptors, Cytoplasmic and Nuclear","Transcription Factors","Transcriptional Activation","Receptor, Farnesoid X-Activated"],"mesh_terms":["Receptor, Farnesoid X-Activated","Animals","Bile Acids and Salts","Cells, Cultured","Cloning, Molecular","DNA-Binding Proteins","Homeostasis","Intestinal Mucosa","Organ Specificity","Transcription Factors","Transcriptional Activation","Receptors, Cytoplasmic and Nuclear","Mice, Knockout","Hepatocytes","Feedback, Physiological","Mice"],"keywords":["CYP8B1","Farnesoid X receptor","Cholesterol 7 alpha-hydroxylase","Liver receptor homolog-1","Small heterodimer partner","Biology","Bile acid","G protein-coupled bile acid receptor","Nuclear receptor","Internal medicine","Endocrinology","Cholic acid","CYP27A1","Cell biology","Transcription factor","Biochemistry","Gene"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T20:52:59.386790Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}