Glutathione and bile acid synthesis. II. Effect of hepatic glutathione content on the activity and mRNA levels of cholesterol 7α-hydroxylase in the rat

Hepatic cholesterol 7α-hydroxylase (CH-7α) activity in intact rats depleted of glutathione (GSH) was reduced significantly (P < 0.007) compared with that in untreated controls. Northern blot analysis of poly A⁺ mRNA isolated from GSH-depleted and control rat livers showed that there was a reduction in mRNA for CH-7α in treated rats that was commensurate with the reduction in CH-7α activity. The fact that the level of transferrin mRNA was unaltered by the depletion of GSH suggests that the change in steady-state CH-7α mRNA content is specifically sensitive to GSH content. This observation extends previous in vitro findings and provides strong justification for a more detailed biochemical investigation into the interaction between GSH levels and the regulation of CH-7α mRNA levels.