Characterization of the bile acid profile in developing male and female hamsters in response to dietary cholesterol challenge

The Syrian golden hamster is a frequently used model to study cholesterol a nd bile acid metabolism as well as cholesterol-induced cholelithiasis. Howe ver, diet-induced gallstones seem limited to young male hamsters of certain strains that develop depressed cholate/chenodeoxycholate bile acid ratios. To further elucidate gender and age specific aspects of cholesterol and bi le acid metabolism. i.e. a possible age-related bile acid,gallstone relatio nship. plasma and biliary lipids and bile acid composition were analyzed in male and female hamsters under various physiological conditions of age and diet, the latter formulated with and without dietary cholesterol. During n ormal development (no cholesterol challenge) the percentage of cholic acid decreased while chenodeoxycholate increased, the shift being more pronounce d in males. Furthermore, female hamsters had higher total plasma cholestero l than in males, while hepatic and biliary lipids did not differ. When chal lenged with excessive dietary cholesterol, female hamsters again developed significantly higher total plasma and hepatic cholesterol concentrations. B iliary lipids and cholesterol gallstone incidence revealed a significant ge nder effect with male hamsters developing a higher lithogenic index and mor e gallstones (cholesterol and pigment stones) than females. Female hamsters revealed a lower percentage of chenodeoxycholate and a higher percentage o f cholate resulting in a more protective. higher cholate/cheno ratio (1.5 /- 1.0) than in males (1.0 +/- 0.2). In summary, the bile acid pattern in d eveloping and cholesterol-fed hamsters renders females less susceptible to gallstones, in part because they maintain more favorable biliary lipid and bile acid profiles, characterized by lower molar percentages of biliary cho lesterol and chenodeoxycholate. (C) 1999 Elsevier Science Inc. All rights r eserved.