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Gender differences in cholesterol nucleation in native bile: estrogen is a potential contributory factor.

Authors
  • Brown, Angela C
  • Wrenn, Steven P
  • Suresh, Nandita
  • Meyers, William C
  • Abedin, Mohammad Z
Type
Published Article
Journal
The Journal of Membrane Biology
Publisher
Springer-Verlag
Publication Date
Dec 01, 2009
Volume
232
Issue
1-3
Pages
35–45
Identifiers
DOI: 10.1007/s00232-009-9214-0
PMID: 19898891
Source
Medline
License
Unknown

Abstract

The incidence of gallstone disease is two to three times higher in women than in men, and female sex hormones, particularly estrogens, have been implicated as contributory factors. Cholesterol nucleation is the initial step in gallstone pathogenesis and proceeds from cholesterol-rich phospholipid vesicles. The aim of this study was to investigate if there is a difference in cholesterol nucleation rates in male and female bile and whether estrogen influences nucleation rates by interacting with cholesterol-rich regions known as "lipid rafts" that exist within the cholesterol-phospholipid vesicles of the bile. Cholesterol nucleation from native prairie dog bile and the interaction of estrogens with lipid rafts in model bile solutions were investigated using Förster resonance energy transfer (FRET). Female native bile samples showed a greater reduction in energy transfer than did male native bile, indicating that cholesterol nucleation occurred more readily in female bile than in male bile. Model bile experiments demonstrated that the addition of estrogen has a significant effect, either cholesterol nucleation or raft disruption, but only in samples containing cholesterol-rich rafts. These results suggest that estrogen interacts with cholesterol-rich rafts in vesicles within bile to promote cholesterol nucleation and predispose females to gallstone formation.

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