Gall‐bladder glycoprotein synthesis and secretion during cholesterol gallstone formation in the mouse

Abstract

Abstract Glycoprotein synthesis by the gall‐bladder was studied during cholesterol gallstone formation in mice fed a diet supplemented with 1% cholesterol and 0.5% cholic acid for up to 6 weeks. Within 1 week, this lithogenic diet induced a 5 fold increase in the cholesterol saturation of gall‐bladder bile, which remained near‐saturated for the next 5 weeks. Cholesterol gallstones were infrequent until the fourth week of the diet. Glycoprotein synthesis was measured as the incorporation of 3H‐glucosamine by mouse gall‐bladder explants in organ culture and was found to double after 4 weeks of the diet when expressed per gall‐bladder. This increase could be explained by a marked enlargement of the gall‐bladder with a greater number of mucus‐secreting cells. Gall‐bladder glycoprotein synthesis and secretion did not appear to be regulated by prostaglandins, since indomethacin blocked prostaglandin synthesis but did not inhibit glycoprotein synthesis. High molecular weight mucin glycoprotein accounted for around one‐third of gall‐bladder glycoprotein secretion.These results are consistent with the hypothesis that gall‐bladder mucin acts as a nucleating agent for cholesterol crystal and gallstone formation. However, this mouse model for cholesterol gallstone formation is different from the prairie dog model, not only in dietary requirements, but also in the effect of the diet on the gall‐bladder, and possibly in the mechanism of regulation of gall‐bladder much glycoprotein synthesis.