The regulation of cholesterol synthesis in human cells

The regulation of HMG-CoA reductase activity and sterol synthesis has been studied in freshly isolated leucocytes. In two kindred, with familial hypercholesterolaemia, three members, one of whom was clinically homozygous, showed normal cellular regulation of sterol synthesis by LDL. This suggests that the abnormality in regulation of sterol synthesis does not invariably reflect the genetic abnormality. With regard to the mechanism of regulation of HMG-CoA reductase by LDL, cordycepin, an inhibitor of mRNA synthesis, had no effect on the induction of sterol synthesis in lymphocytes incubated in medium containing lipid-depleted serum although the drug inhibited mRNA synthesis by more than 50 per cent. This suggests that LDL-derived cholesterol may regulate HMG-CoA reductase at a post-transcriptional level.