Defective 3-ketosteroid reductase activity in a human monocyte-like cell line

The human monocyte-like cell line U937, which is a cholesterol auxotroph, does not grow on mevalonate, squalene, or 4,4-dimethyl cholest-7-en-3/3-01. It grows on cholest-7-en-3P- 01 and converts it to cholesterol. When deprived of an exogenous source of cholesterol, the cells accumulate 4a-methyl-cholest- 8-en-3-one. The cell-free extracts of U937 are also devoid of 3- ketoreductase activity. The present studies indicate that the le- sion in cholesterol synthesis by these cells is located at 3-ketosteroid reductase, making this the first report of a deficien- cy of this enzyme. In contrast, another U937 strain (U937-N) synthesizes cholesterol, does not accumulate 4a-methyl-cholest- 8-en-3-one, and has 3-ketosteroid reductase activity. The two strains should be valuable in studies of the regulation of cholesterol metabolism and of the role of cholesterol in mem- brance structure and function.-Billheimer, J. T., D. Cha- moun, and M. Esfahani. Defective 3-ketosteroid reductase activity in a human monocyte-like cell line. J. Lipid Res. 1987. 28: 704 - 709. Supplementary key words 4~-methyl-cholest-8-en-3-one macro- phage-like U937 cells