Relative rates of sterol synthesis in the liver and various extrahepatic tissues of normal and cholesterol-fed rabbits. Relationship to plasma lipoprotein and tissue cholesterol levels

The relative rates of sterol synthesis in the liver and ten extrahepatic tissues of normal and cholesterol-fed rabbits were determined by measuring the rates of incorporation of [l-₁₄C]octanoate into digitonin-precipitable sterols by tissue slices. In normal rabbits the rate of sterol synthesis in the liver was very low compared to that in several extrahepatic tissues, particularly the small intestine. The rate of synthesis in the small intestine showed marked regional variation, with the highest rate occurring in the section proximal to the entry of the common bile duct and the lowest rate in the mid-sections of the intestine. The regional differences in intestinal sterol synthesis correlated inversely with the cholesteryl ester content of the tissue. Rabbits fed the cholesterol diet developed marked hypercholesterolemia, with much of the additional cholesterol appearing in the VLDL and LDL fractions. The cholesteryl ester content of the liver, small intestine and various other extrahepatic tissues increased significantly. Coincident with these changes was a marked suppression of sterol synthesis, not only in the liver, but also in the small intestine, adrenal gland, kidney, lung, spleen and ovary. Thus, the rabbit, like the guinea pig, normally exhibits a very low rate of hepatic sterol synthesis compared to that found in other species such as the rat, squirrel monkey and baboon and, furthermore, manifests feedback inhibition of both hepatic and extrahepatic sterol synthesis when dietary cholesterol intake is increased. This general suppression of synthesis correlates with an accumulation of cholesteryl ester in the tissues which, in turn, presumably is related to the uptake of lipoprotein cholesterol from the hypercholesterolemic plasma that develops under such dietary conditions.