Hormonal effects upon in vitro cholesterol synthesis.

CONNECTIVE tissue isolated from the albino rat by the sponge implantation technic is rich in lipids and has a high concentration of cholesterol. It has been demonstrated that aortic tissue of the rabbit and chicken can synthesize cholesterol in vitro from C-labeled acetate. Connective tissuesponge biopsies from the albino rat synthesize cholesterol in vitro at a rate which is comparable to that reported for aortic tissue. Considerable interest in the mechanism of cholesterol accumulation in the arterial wall has resulted from the observations that a distorted serum lipid partitioning occurs in human atheromatosis and that serum lipids may be altered by the administration of certain hormones. The earliest biochemical changes in the intima as atherosclerosis develops in the human are increases in the amount of collagen and in the binding of hexosamine by the scleroprotein of intimal connective tissue. There is a sex difference in the lipid partitioning in the human atheroma. Furthermore, atherosclerotic changes in arteries occur more commonly in the human male than in the female. Thus, the relationship of the effects of sex hormones upon cholesterol synthesis in connective tissue to the problem of atherosclerosis is fundamental. The purpose of this investigation was to study (a) the incorporation of C-labeled acetate into cholesterol and other digitoninprecipitable substances in slices of connective tissue and liver, and (b) the effects of certain