Induction of HMG CoA reductase by the administration of 20,25-diazacholesterol

This paper describes the direct examination of HMG CoA reductase activity in rats treated with 20,25-diazacholesterol. Conversion of acetyl CoA and HMG CoA to mevalonate increased to over 200% of control values in the microsomes and in the 12,000 g supernatant of liver homogenates after 5 days of treatment. The time course of induction coincided with the development of hypocholesterolemia. Animal weights, liver weights, and microsomal protein content did not vary significantly between animal groups. Incubations to which the compound was introduced in vitro in concentrations as great as 0.5 mM produced no significant difference from control incubations. Similar treatment of the animals with 7-ketocholesterol, a cholesterol derivative reported to repress HMG CoA reductase activity in tissue cultures, produced no appreciable difference in reductase activity or serum steroid levels in vivo.