Regulation of sterol synthesis in 15 tissues of rat. II. Role of rat and human high and low density plasma lipoproteins and of rat chylomicron remnants

These studies were undertaken to identify which, if any, of the circulating lipoproteins regulates sterol synthesis in various extrahepatic organ systems. Following administration of 4 aminopyrazolo [3,4 d] pyrimidine to rats for 72 h, the plasma cholesterol level fell to <10 mg x dl^-1 and sterol synthesis in 9 of 15 extrahepatic tissues increased 1.8- to 34.9-fold. Infusion of a preparation of either human or rat 'whole' plasma lipoproteins, i.e. a fraction containing all plasma lipoproteins with a density of <1.230, over a 40 h period to similarly treated animals suppressed synthesis in nearly all of these tissues, indicating that one or more of the specific lipoproteins in this fraction were responsible for suppression of synthesis in at least these tissues. With a similar experimental protocol, the infusion of low density lipoproteins (LDL) suppressed synthesis in most of the tissues tested (such as gut, kidney, and lung), whereas infusion of high density lipoproteins (HDL) or chylomicron remnants had no suppressive effect on synthesis in this group of tissues. In contrast, sterol synthesis in ovary and adrenal gland was markedly suppressed by HDL and, to a lesser degree, by chylomicron remnants. LDL had no effect on sterol synthesis in the ovary but did produce modest suppression in the adrenal gland. On the basis of these studies and other published reports, three functionally different types of lipoprotein feedback regulation of sterol synthesis are proposed: regulation of hepatic cholesterogenesis by chylomicron remnants; regulation of sterol synthesis in a number of nonendocrine, extrahepatic tissues by LDL; and regulation of sterol synthesis in ovary and adrenal gland principally by HDL.