BIOSYNTHESIS OF CHOLESTEROL 391 



the sterol available from exogenous sources, being high when no cholesterol 

 is present in the food, and decreased as increasing amounts of the sterol 

 are supplied in the diet. This mechanism operates to maintain the body 

 cholesterol at a relatively constant value. 



The above observations on the control of cholesterol synthesis have been 

 confirmed by more recent work. Tomkins and Chaikoff^^^ reported that 

 the rate of cholesterol synthesis from acetate by rat liver slices is a function 

 of the cholesterol intake of the animals from which the liver was obtained. 

 Thus, when a diet containing 5% of cholesterol was fed to rats for eight 

 days prior to death, the rate of cholesterol synthesis in the liver was prac- 

 tically O; likewise, when the animals were fed diets containing only 0.5% 

 of cholesterol for seven days, a marked depression in cholesterol production 

 was noted. Even a single feeding of this alcohol was sufficient to produce 

 an inhibitory effect. These authors postulate that the rate of cholesterol 

 synthesis in the liver is subject to homeostatic regulation by dietary choles- 

 terol.-^^ Frantz et al.-^^ presented similar data on the rat, and indicated 

 that the inhibition of cholesterol synthesis is a function of the level of liver 

 cholesterol; apparently it is not mediated through the thyroid gland. 

 Langdon and Bloch-" also confirmed the inhibitory effect of dietary choles- 

 terol on the rate of cholesterol synthesis. Alfin-Slater and associates'^^ 

 observed that cholesterol synthesis was still suppressed in the livers of rats 

 eight days after the cessation of cholesterol feeding when the subsequent 

 diet had been a fat-free one; however, when high-fat diets were fed after 

 the termination of cholesterol feeding, the rate of cholesterol synthesis re- 

 turned to normal within eight days. Although the experimental evidence 

 that cholesterol feeding reduces the synthesis of cholesterol in the liver is 

 Cjuite convincing, Gould et al.^^^ found that a similar inhibition in the rate 

 of synthesis of cholesterol did not occur in the skin or intestinal mucosa as 

 the result of cholesterol administration. 



d. The Administration of Cholesterol-Like Compounds. Two differ- 

 ent effects of cholesterol-like compounds have been observed, namely, 

 that which occurs when readily absorbed sterols and related substances are 

 fed, and that which is observed when the soy sterols and other related dif- 

 ficultly absorbed products are given. 



"5 G. M. Tomkins, H. Sheppard, and I. L. Chaikoff, /. Biol. Chem., 201, 137-141 

 (1953). 



"6 1. D. Frantz, Jr., H. S. Schneider, and B. T. Hinkelman, /. Biol. Chem., 206, 465- 

 469(1954). 



2" R. G. Langdon and K. Bloch, J. Biol. Chem., 202, 77-81 (1953). 



"8 R. B. Alfin-Slater, M. C. Schotz, F. Shimoda, and H. J. Deuel, Jr., /. Biol. Chem., 

 195, 311-315(1952). 



"' R. G. Gould, C. B. Taylor, J. S. Hagerman, I. Warner, and D. J. Campbell, 

 J. Biol. Chem., 201, 519-528 (1953). 



