HMG CoA reductase and LDL receptor genes are regulated differently by 15-ketosterols in Hep G2 cells

The ability of two 15-ketosubstituted sterols, 5 alpha-cholest-8(14)- en-3 beta-ol-15-one and 3 beta-(2-hydroxyethoxy)5a-cholest-8(14)-en-15-one, to a lter the mRNA levels of 3-hydroxy-3-methylglutaryl-CoA reductase, low densi ty lipoprotein receptor, and oxysterol binding protein was studied and comp ared with the effects of 25-hydroxycholesterol in Hep G2 cells. All three o xysterols decreased the level of HMG CoA reductase mRNA at concentrations o f 10-30 mu M, although 25-hydroxycholesterol was effective at concentration s of 1-3 mu M. 25-Hydroxycholesterol lowered the level of LDL receptor mRNA more efficiently after 8 hours than after 24 hours of incubation, whereas 15-ketosterols did not decrease the mRNA level of the LDL receptor. The tra nscriptions of HMG CoA reductase and LDL receptor genes are therefore indep endently regulated by 15-ketosterols in Hep G2 cells. In addition, the leve l of the oxysterol binding protein mRNA is not affected by oxysterols in He p G2 cells. (C) 1999 Academic Press.