We used squirrel monkeys (Saimiri sciureus) as models to investigate human sex differences in susceptibility to cholesterol gallstones, biliary function, and plasma lipoproteins. Cholesterol gallstones developed in a large proportion of intact and gonadectomized male and female Brazilian monkeys maintained on a lithogenic diet, but male Bolivian monkeys were completely resistant. Although the gallbladder bile of nearly all monkeys was saturated with cholesterol, the bile of the Bolivian monkeys had a much greater concentration of total lipids (cholesteriol + phospholipid + bile acids) than did bile of the other groups. The male Bolivian monkeys had the highest percentage of gallbladder bile acids as chenodeoxycholic and the lowest as deoxycholic acids. They also had larger total body pools of cholic and chenodeoxycholic acids than any other group. The lithogenic index of all Brazilian squirrel monkeys with gallstones was greater than that of all Brazilian monkeys that were free of stones. The level of HDLs was much lower in the plasma of Bolivian monkeys than in that of any group of Brazilian monkeys, and the differences were restricted to the HDL2 subfraction. Addition of cholesterol (0.9 mg/Kcal) to the regular semipurified diet containing butter resulted in elevations in the LDLs of all groups and a change in the relative compositions of HDL and LDL (a higher percentage of cholesterol and lower percentage of protein). The occurrence of low plasma HDL2 levels in a population of squirrel monkeys resistant to cholesterol gallstones is consistent with the suggested role of that fraction in net transport of cholesterol to the bile.

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