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

Abstract

The synthesis of cholesterol has been demon- strated in virtually every tissue of the mammalian body with the important exception of the mature nervous system (1). Yet studies in this field have primarily centered about cholesterogenesis in the liver for at least two important reasons: first, early reports suggested that the liver was the sole endogenous source of circulating cholesterol (2), and secondly, the rate of hepatic cholesterol synthesis was shown to be controlled by a sensitive feedback mechanism of considerable practical and theoretical interest (3, 4). By contrast, little information is available concerning either the physiologic im- portance or the means of regulation of cholesterogenesis in the intestine. Yet the recent report of Lindsey and Wilson (5), which unequivocally demonstrates that the intestine contributes to the circulating cholesterol pool, emphasizes the need for a more thorough evaluation of cholesterol synthesis by the gastrointestinal tract. The present studies, therefore, were undertaken to investigate three aspects of intestinal sterol synthesis: 1) char- acterization of synthetic rates along the length of the gastrointestinal tract, 2) localization of the syn- thetic site within the small bowel wall, and 3) eval- uation of mechanisms operative in the control of intestinal cholesterogenesis.