New insights into the molecular mechanisms underlying effects of estrogen on cholesterol gallstone formation

Helen H. Wang, Min Liu, Deborah J. Clegg, Piero Portincasa, David Q.H. Wang

Research output: Contribution to journalReview article

57 Scopus citations

Abstract

Epidemiological and clinical studies have found that at all ages women are twice as likely as men to form cholesterol gallstones, and this gender difference begins since puberty and continues through the childbearing years, which highlight the importance of female sex hormones. Estrogen is a crucial hormone in human physiology and regulates a multitude of biological processes. The actions of estrogen have traditionally been ascribed to two closely related classical nuclear hormone receptors, estrogen receptor 1 (ESR1) and ESR2. Recent studies have revealed that the increased risk for cholesterol gallstones in women vs. men is related to differences in how the liver metabolizes cholesterol in response to estrogen. A large number of human and animal studies have proposed that estrogen increases the risk of developing cholesterol gallstones by increasing the hepatic secretion of biliary cholesterol, which, in turn, leads to an increase in cholesterol saturation of bile. Furthermore, it has been identified that hepatic ESR1, but not ESR2, plays a major role in cholesterol gallstone formation in mice in response to high doses of 17β-estradiol. The mechanisms mediating estrogen's action have become more complicated with the recent identification of a novel estrogen receptor, G protein-coupled receptor 30 (GPR30), a member of the seven-transmembrane G protein-coupled receptor superfamily. In this review, we provide an overview of the evidence for the lithogenic actions of estrogen through ESR1 and discuss the cellular and physiological actions of GPR30 in estrogen-dependent processes and the relationship between GPR30 and classical ESR1 on gallstone formation.

Original languageEnglish (US)
Pages (from-to)1037-1047
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1791
Issue number11
DOIs
StatePublished - Nov 1 2009
Externally publishedYes

Keywords

  • Bile
  • Bile salt
  • Crystallization
  • Estrogen
  • Estrogen receptor
  • Female gender
  • G protein-coupled receptor

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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