Inhibition of cholesterol synthesis in mammary tissue, lung, and kidney following cholesterol feeding in the lactating rat.

Pregnant rats were randomly allocated to one of 3 experimental dietary groups: Group 1 -- 15.5% butter, 2% cholesterol, 0.78% sodium cholate purified diet; Group 2 -- standard rat diet with the addition of 10% lard and 2% cholesterol, and Group 3 -- standard rat diet. Plasma and milk cholesterol at 10 days postpartum were significantly elevated in dams fed exogenous cholesterol. The rat of incorporation of [1-14C] acetate into digitonin-precipitable sterols of mammary tissue slices from dams in Group 1 and Group 2 was eight-fold and two-fold, respectively, less than controls. Mammary tissue cholesterol was greater in dams fed detary cholesterol. Thus, our data, for the first time, demonstrate that cholesterol synthesis in lactating rat mammary tissue is suppressed following cholesterol feeding. In a second experiment, the rate of incorporation of [1-14C] acetate into digitonin-precipitable sterols in kidney and lung tissue of Group 1 rats was suppressed; however, this response was not as marked as that observed in lactating mammary tissue. The concentration of cholesterol in kidney and lung was greater than controls. These results suggest that extrahepatic inhibition of cholesterol synthesis exists in the rat with a concomitant increase in tissue cholesterol.