De novo sterologenesis in the intact rat

On the basis mainly of in vitro studies, the liver and, to a lesser degree, the small intestine are widely accepted as the major sites of de novo sterologenesis. Utilizing [3H]water, we have investigated de novo sterologenesis in intact rats. Greater than 80% of labeled nonsaponifiable lipids and more than 70% of the labeled cholesterol were localized to extrahepatic, extraintestinal tissues. Feeding cholesterol markedly suppressed hepatic sterologenesis but had little influence on extrahepatic sites of sterol synthesis. Similarly, partial hepatectomy, which greatly decreased sterol synthesis in the liver, also did not significantly affect the accumulation of labeled sterols in extrahepatic tissues; therefore, the transport of sterols from the liver did not account for a significant portion of labeled sterols in extrahepatic tissues. Cannulation of the thoracic duct demonstrated that transport of newly synthesized intestinal sterols to peripheral tissues also did not account for the large accumulation of labeled sterols in extrahepatic, extraintestinal tissues. The primary extrahepatic, extraintestinal sites of sterologenesis were the skin and remaining carcass. The lung, kidney, spleen, heart, ovary, brain, muscle and adipose tissue made minor contributions to de novo sterol synthesis. Therefore, tissues other than the liver and intestine, especially the skin and remaining carcass, are important sites of de novo sterologenesis in vivo.