Regulation of sterol synthesis in 16 tissues of rat. I. Effect of diurnal light cycling, fasting, stress, manipulation of enterohepatic circulation, and administration of chylomicrons and triton

The rate of cholesterol synthesis in the liver is affected by many physiological variables. This study was undertaken to measure systematically the effect of these same variables on sterol synthesis in 15 extrahepatic tissues of the rat. Diurnal light cycling caused a significant change in the rate of cholesterogenesis in the liver but had no effect on the rate of sterol synthesis in any of the extrahepatic tissues tested. Fasting markedly reduced the rate of hepatic cholesterol synthesis and resulted in lesser degrees of reduction in the rate of sterol synthesis in kidney, intestine, and several other tissues. Experimental manipulations designed to alter markedly the amount of bile acid circulating in the enterohepatic circulation (such as biliary diversion, biliary obstruction, and cholestyramine or bile acid feeding) had no effect on the rate of sterol synthesis in any tissue assayed except the liver, intestine, and adrenal gland. Administration of chylomicrons intravenously caused significant suppression of the rate of cholesterol synthesis in the liver but not in any other tissue. In contrast, the administration of Triton 1339 enhanced sterol synthesis not only in liver but also in intestine, colon, kidney, lung, spleen, and, especially, adrenal gland. The liver and adrenal gland, but not the other tissues, also responded to stress with enhanced synthesis. These studies emphasize that rates of sterol synthesis in a number of extrahepatic tissues do change in response to specific physiological variables. In addition, these data suggest that chylomicrons play no role in the regulation of sterol synthesis in any tissue but the liver, while the results with Triton 1339 administration raise the possibility that sterol synthesis in several extrahepatic tissues may be regulated by one or more of the circulating serum lipoprotein fractions.