{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T02:35:20Z","timestamp":1792204520581,"version":"4.4.0"},"reference-count":41,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,10,22]],"date-time":"2020-10-22T00:00:00Z","timestamp":1603324800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Estrogen is an important risk factor for cholesterol gallstone disease because women are twice as likely as men to form gallstones. The classical estrogen receptor \u03b1 (ER\u03b1), but not ER\u03b2, in the liver plays a critical role in the formation of estrogen\u2010induced gallstones in female mice. The molecular mechanisms underlying the lithogenic effect of estrogen on gallstone formation have become more complicated with the identification of G protein\u2013coupled receptor 30 (GPR30), an estrogen receptor.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We investigated the biliary and gallstone phenotypes in ovariectomized female GPR30<jats:sup>\u2212\/\u2212<\/jats:sup>, ER\u03b1<jats:sup>\u2212\/\u2212<\/jats:sup>, and wild\u2010type mice injected intramuscularly with the potent GPR30\u2010selective agonist G\u20101 at 0 or 1\u00a0\u03bcg\/day and fed a lithogenic diet for 8\u00a0weeks. The activation of GPR30 by G\u20101 enhanced cholelithogenesis by suppressing expression of cholesterol 7\u03b1\u2010hydroxylase, the rate\u2010limiting enzyme for the classical pathway of bile salt synthesis. These metabolic abnormalities led to an increase in biliary cholesterol concentrations in company with hepatic hyposecretion of biliary bile salts, thereby inducing cholesterol\u2010supersaturated gallbladder bile and accelerating cholesterol crystallization. G\u20101 also impairs gallbladder emptying, leading to sluggish gallbladder motility and promoting the development of biliary sludge in the early stage of gallstone formation. The prevalence rates of gallstones were 80% in wild\u2010type and ER\u03b1<jats:sup>\u2212\/\u2212<\/jats:sup> mice treated with G\u20101 compared to 10% in wild\u2010type mice receiving no G\u20101. However, no gallstones were formed in GPR30<jats:sup>\u2212\/\u2212<\/jats:sup> mice treated with G\u20101.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>GPR30 produces additional lithogenic actions, working independently of ER\u03b1, to increase susceptible to gallstone formation in female mice; both GPR30 and ER\u03b1 are potential therapeutic targets for cholesterol gallstone disease, particularly in women and patients exposed to high levels of estrogen.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31212","type":"journal-article","created":{"date-parts":[[2020,2,29]],"date-time":"2020-02-29T08:30:18Z","timestamp":1582965018000},"page":"2077-2089","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":41,"title":["Activation of Estrogen Receptor G Protein\u2013Coupled Receptor 30 Enhances Cholesterol Cholelithogenesis in Female Mice"],"prefix":"10.1097","volume":"72","author":[{"given":"Helen H.","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Medicine and Genetics,Division of Gastroenterology and Liver Diseases,Marion Bessin Liver Research Center,Einstein\u2010Mount Sinai Diabetes Research Center,Albert Einstein College of Medicine,Bronx,NY"},{"name":"Department of Internal Medicine,Division of Gastroenterology and Hepatology,Saint Louis University School of Medicine,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ornella","family":"de Bari","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine,Division of Gastroenterology and Hepatology,Saint Louis University School of Medicine,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher K.","family":"Arnatt","sequence":"additional","affiliation":[{"name":"Department of Chemistry,Saint Louis University,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine,University of Cincinnati College of Medicine,Cincinnati,OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Portincasa","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences and Human Oncology,Clinica Medica \u201cA. 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