Effect of lithocholic acid on cholesterol synthesis and transport in the rat liver.

The cellular origin of cholesterol which accumulates in liver cell plasma membrane fractions enriched in bile canalicular structures after lithocholic acid treatment was determined in vivo. Rats were given [3H]cholesterol followed 16 h later by [2-14C]mevalonic acid, [2-14C]acetic acid or lithocholic acid. Lithocholic acid injection enhanced the de novo synthesis of cholesterol in the microsomes and both compounds were transported to the bile canalicular membranes. However, in vitro studies demonstrated that lithocholic acid is capable of stripping cholesterol from microsomal membranes even in the absence of increased de novo synthesis. This suggests that transfer of cholesterol from subcellular organelles (microsomes) to bile canalicular membranes may be the initial step in the development of lithocholic acid-induced cholestasis.