GLUTATHIONE AND BILE-ACID SYNTHESIS .2. EFFECT OF HEPATIC GLUTATHIONECONTENT ON THE ACTIVITY AND MESSENGER-RNA LEVELS OF CHOLESTEROL 7-ALPHA-HYDROXYLASE IN THE RAT

Hepatic cholesterol 7alpha-hydroxylase (CH-7alpha) activity in intact rats depleted of glutathione (GSH) was reduced significantly (P < 0.00 7) 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-7alpha in treated rats that was commensurate with the reduction in CH-7alpha activity. The fact t hat the level of transferrin mRNA was unaltered by the depletion of GS H suggests that the change in steady-state CH-7alpha mRNA content is s pecifically sensitive to GSH content. This observation extends previou s in vitro findings and provides strong justification for a more detai led biochemical investigation into the interaction between GSH levels and the regulation of CH-7alpha mRNA levels.