HORMONES AND CHOLESTEROL ESTER METABOLISM

A bstract A study was made of the effects of testosterone, estradiol, ACTH, insulin, epinephrine and l ‐thyroxine on a microsomal preparation of female rat liver esterifying enzyme and cholesterol plus palmitic, oleic and linoleic acids. In the doses used, these hormones modified the rate of ester synthesis. Further experiments showed that low doses of androgen or estrogen had a stimulating effect whereas high doses had an inhibitory effect. On the basis of our findings and a review of the literature, it is concluded that the concentration of cholesterol or its esters in the plasma at any given time is determined by the net rate: 1) of absorption, 2) synthesis, 3) transport and lipoprotein binding, and 4) fecal excretion and partial re‐absorption following oxidative degradation of cholesterol to bile acids. The turnover rate of free cholesterol is far more rapid than that of the ester. Also, the degree of unsaturation of the ester influences the rate of turnover. Mono‐unsaturated esters have the highest turnover rate. Lipoprotein binding in the very‐low‐density fraction is dependent upon diet; the more dense lipoproteins (> 1.061–1.21) are thought to be partially under genetic control. Hormones act at three levels: 1) biosynthesis, 2) compartmentalization and transport (binding), and 3) excretion. The first two mechanisms may be involved with androgens, estrogens and insulin. The atherosclerotic process involves many physicochemical factors. Diet and hormones modify the ester fraction. They also change the endogenous synthesis of cholesterol from acetate or mevalonate. Apparently the composition of the ester plays an important role in the deposition of cholesterol and its esters in sites of predilection.