Activation of Estrogen Receptor G Protein–Coupled Receptor 30 Enhances Cholesterol Cholelithogenesis in Female Mice

• DOI: 10.1002/hep.31212
• Publication Date: 2020-02-29T08:30:18Z
• Authors: Helen H. Wang; Ornella de Bari; Christopher K. Ar...; Min Liu; Piero Portincasa; David Q.‐H. Wang
• Keywords: GPER

Background and Aims Estrogen is an important risk factor for cholesterol gallstone disease because women are twice as likely men to form gallstones. The classical estrogen receptor α (ERα), but not ERβ, in the liver plays a critical role formation of estrogen‐induced gallstones female mice. molecular mechanisms underlying lithogenic effect on have become more complicated with identification G protein–coupled 30 (GPR30), receptor. Approach Results We investigated biliary phenotypes ovariectomized GPR30 −/− , ERα wild‐type mice injected intramuscularly potent GPR30‐selective agonist G‐1 at 0 or 1 μg/day fed diet 8 weeks. activation by enhanced cholelithogenesis suppressing expression 7α‐hydroxylase, rate‐limiting enzyme pathway bile salt synthesis. These metabolic abnormalities led increase concentrations company hepatic hyposecretion salts, thereby inducing cholesterol‐supersaturated gallbladder accelerating crystallization. also impairs emptying, leading sluggish motility promoting development sludge early stage formation. prevalence rates were 80% treated compared 10% receiving no G‐1. However, formed Conclusions produces additional actions, working independently ERα, susceptible mice; both potential therapeutic targets disease, particularly patients exposed high levels estrogen.