Origin of milk cholesterol in the rat: dietary versus endogenous sources

Slices of mammary gland from lactating rats, incubated with acetate-1-(14)C or mevalonate-2-(14)C, synthesized cholesterol-(14)C. Within 2 min of an intravenous injection of 1 ml of a suspension of chylomicrons containing cholesterol-4-(14)C, mammary glands of lactating rats removed as much as 29% of the labeled cholesterol; those of 2-day-postlactating rats removed none. Rats were fed a diet containing 0.05% cholesterol-4-(14)C from 7 days prepartum to 20 days postpartum. At isotopic equilibrium, the relative specific activities of milk and dietary cholesterol indicated a dietary origin for 11% of the milk cholesterol. The extent to which endogenous sources-liver and mammary gland-contributed cholesterol to milk proved entirely dependent on whether dietary cholesterol, in the form of chyle lipo-proteins, was first processed by liver or taken up directly by mammary gland. Lack of information regarding the extent to which chyle cholesterol is removed from blood under physiological conditions by mammary gland and other tissues precludes precise assessment of the endogenous contributions to milk cholesterol and, moreover, casts doubt on the quantitative interpretability of cholesterol-(14)C-feeding experiments reported in the literature.