Loss of the Cholesterol Feedback System in the Intact Hepatoma-Bearing Rat

Abstract

By means of the desmosterol suppression technique described in the previous paper, the influence of hepatomas on sterol metabolism has been studied in the intact rat. The major finding of this study is that all hepatoma-bearing rats demonstrate a consistent in vivo loss of the cholesterol feedback system that is characteristic of normal liver. The results also demonstrate that such tumors retain only minor amounts of the sterol they synthesize, releasing over 90% of such endogenous sterol into the circulation. Finally, the in vivo loss of cholesterol feedback control was found to occur in at least two minimal deviation hepatomas and in one highly malignant adenocarcinoma of hepatic origin. These findings indicate that even tumors that are capable of only very limited cholesterol synthesis in vitro, can contribute significant quantities of sterol to the bloodstream. It is concluded that as a result of their lack of normal cholesterol feedback control, hepatomas may represent a physiologically important source of sterols in the tumor-bearing animal, and that the absence of feedback control of sterol synthesis may provide a means of detecting the presence of such tumors in the intact animal.