Cholesterol synthesis by the gastrointestinal tract: localization and mechanisms of control.

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Abstract
Three aspects of sterol synthesis by the gastrointestinal tract of the rat are studied. The relative synthetic rates along the length of esophagus, stomach, and small and large bowel, localization of the site of cholestero-genesis within the wall of the small intestine, and possible mechanisms responsible for physiologic control of intestinal sterol synthesis. The synthesis of digitonin precipitable sterols occurred at every level of the gastrointestinal tract; however, the synthetic rate in the esophagus, proximal small bowel, and proximal colon was relatively low when compared to the active rates of synthesis found in the stomach, ileum, and distal colon. When the wall of the small intestine was subdivided into 3 tissue layers, sterol synthetic activity was almost exclusively found in the tissue preparation containing the intestinal crypts; by contrast the intestinal villi and smooth muscle were essentially devoid of synthetic activity. Neither cholesterol feeding nor fasting significantly altered the rate of intestinal sterol synthesis. Bile, however, was shown to contain a potent inhibitor that acts directly upon the intestinal mucosa to suppress cholesterogenesis. The importance of this inhibitor as a determinant of the normal variation in the rate of sterol synthesis along the length of the small bowel is discussed.