Estrogen induces two distinct cholesterol crystallization pathways by activating ERα and GPR30 in female mice

• DOI: 10.1194/jlr.m059121
• Publication Date: 2015-07-08T02:21:19Z
• Authors: Ornella de Bari; Tony Y. Wang; Min Liu; Piero Portincasa; David Q-H. Wang
• Keywords: GPER

To distinguish the lithogenic effect of classical estrogen receptor α (ERα) from that G protein-coupled 30 (GPR30), a new receptor, on estrogen-induced gallstones, we investigated entire spectrum cholesterol crystallization pathways and sequences during early stage gallstone formation in gallbladder bile ovariectomized female wild-type, GPR30((-/-)), ERα((-/-)), GPR30((-/-))/ERα((-/-)) mice treated with 17β-estradiol (E2) at 6 µg/day fed diet for 12 days. E2 disrupted biliary salt metabolism through ERα GPR30, leading to supersaturated predisposing precipitation monohydrate crystals. In GPR30((-/-)) mice, arc-like tubular crystals formed first, followed by parallelogram-shaped ERα((-/-)) lamellar liquid crystals, typified birefringent multilamellar vesicles, appeared earlier than Both were accelerated wild-type activation GPR30 E2. However, was drastically retarded mice. We concluded activates produce crystalline versus anhydrous metastable intermediates evolving bile. produces synergistic action enhance E2-induced formation.