A critical step in the formation of
cholesterol gallstones in nucleation (i.e., the formation of
cholesterol monohydrate crystals from supersaturated bile). The rate of nucleation of
cholesterol depends upon a critical balance between pronucleating and antinucleating factors in bile.
Mucin, a high molecular weight
glycoprotein secreted by the gallbladder and biliary duct epithelium, is a pronucleating agent in experimental and human
gallstone disease. Gallbladder
mucin shares with other epithelial
mucins the ability to bind
lipids and
bile pigment. The hydrophobic binding sites in the
polypeptide core of
mucin may provide a favorable environment for nucleation of
cholesterol monohydrate from supersaturated bile. In nearly all animal models of
cholelithiasis,
mucin hypersecretion is prominent. The stimulus for gallbladder
mucin hypersecretion appears to be a component of lithogenic bile.
Prostaglandins regulate
mucin release in gallbladder epithelium in vitro and probably in vivo. In the
cholesterol-fed prairie dog, blockage of
mucin release with
aspirin inhibits
gallstone formation. These findings suggest that inhibition of
mucin release may prevent
cholesterol stone formation during high-risk periods or after dissolution
therapy with
bile salts.