The work to be carried out will be concerned with the relationship between the effects of glucocorticoids on cholesterol biosynthesis and the regulation of cell growth. It will consist of a study of the two key enzymes viz. 3-hydroxy-3-methyl-glutaryl coenzyme A synthase and 3-hydroxy-3-methylglutaryl coenzyme A reductase and the involvement of dexamethasone in their regulation through the synthesis of activators and inhibitors. An attempt will be made to relate changes in the levels of those enzymes to the cell cycle. The project will also include a study of the cell variants resistant to polyene antibiotics which usually contain much less cellular cholesterol than the wild population. Although this investigation will initially involve epithelioid cell lines, it will be extended to include human lymphoid cells. The objective is to study the role of cholesterol as a controlling factor in cellular growth and to understand the role of glucocorticoids as pleiotypic growth regulators. The methods to be used will include isotopic enzyme assays, various analytical procedures for lipid determination and extensive use of flow microfluorometry.
NIH ExPorter
NIH ExPorter