Studies will be centered around a cytosolic protein that binds oxysterols which are specific suppressors of MHG-CoA reductase. Assays for the binding protein will be improved, physical-chemical properties of the protein, kinetic characteristics of the binding reaction and relationships between binding and sterol structure will be investigated. Attempts to purify the protein will be made. Other investigations will be concerned with the role of the binding protein in the regulation of HMG-CoA reductase. Translocation of the sterol-protein complex to the nucleus will be studied. Measurements of binding protein levels will be made in various tissues and cells, in vivo wherein the level of HMG-CoA reductase varies. These tissue include cultured cells, tumors, liver muscle, intestine, and differentiating erythropoietic cells, brain, and testes. The occurrence in cells of regulatory oxysterols will be investigaged by testing sterols extracted from cells and fractionated by thin-layer chromatography for their ability to displace (3H)25-hydroxycholesterol from the binding protein. Additional studies, utilizing compactin, 25-hydroxycholesterol, cycloheximide will be aimed at determining the extent to which each compound affects the synthesis and the degradation of HMG-CoA reductase.