Control of cholesterol synthesis in hepatomas: Absence of diurnal rhythm in hepatomas 7794A and 9618A

Abstract

We have examined the Morris hepatomas 7794A and 9618A for the presence of a diurnal variation in cholesterol synthesis such as is observed in the livers of normal rats. Whereas the livers of the tumour-bearing animals showed a 3–5 fold increase in rate of cholesterol synthesis from acetate between midday and midnight, no such increase occurred in the hepatomas. Furthermore, adrenalectomy resulted in a 3-fold increase in cholesterol synthesis (as measured at midday) in the host liver, but not in hepatoma 7794A. Work by others has indicated that diurnal variations in cholesterol synthesis in normal liver are due to variations in the amount rather than in the specific activity of the ratecontrolling enzyme of the cholesterogenic pathway, namely β-hydroxy-β-methylglutaryl co-enzyme A reductase. Our work has now demonstrated that at least two of the “minimal-deviation” hepatomas exhibit a defect in control over the synthesis and/or degradation of this enzyme, i.e. in addition to the defective “feedback” control of its activity that has been shown in many previous reports.