Increases in gallbladder prostaglandin synthesis before the formation of cholesterol gallstones

Abstract

Increased synthesis of prostaglandins in the wall of the gallbladder may play a role in the pathogenesis of cholesterol gallstones by mediating mucus hypersecretion and thereby accelerating nucleation and the precipitation of cholesterol-supersaturated bile. We induced gallstones in prairie dogs and guinea pigs by feeding a cholesterol-supplemented diet for periods as long as 6 weeks. Gallbladder prostaglandin synthesis was quantitated by specific radioimmunoassays that measured the amount of various prostanoids released from the gallbladder during in vitro incubation. The gallbladders of cholesterol-fed prairie dogs showed increased synthesis of prostaglandin E2, prostaglandin F2a, and thromboxane and increased concentrations of glycoprotein in gallbladder bile. These changes were evident as early as 2 weeks after institution of the cholesterol diet, although cholesterol gallstones did not form until 4 or more weeks. In contrast, cholesterol feeding of the guinea pig did not induce cholesterol supersaturation. In this species pigment gallstones formed, probably as a result of a cholesterol-induced hemolytic anemia, and gallbladder mucus hypersecretion did not occur. Pigment gallstone formation in the guinea pig was associated with an increase in prostacyclin synthesis, but the synthesis of prostaglandin F2a and thromboxane was decreased. Increased prostaglandin synthesis may contribute to the formation of cholesterol gallstones but does not appear to participate in pigment gallstone formation.