Abstract
It has been reported that administration of orally-active steroids such as norethandrolone (1, 2), norethisterone (3), methyltestosterone (4) and methandienone (5) can cause in some patients a type of cholestatic jaundice characterized by accumulation of bile in the liver without extrahepatic biliary obstruction (intrahepatic cholestasis), occurence of canalicular bile-plugs, absence of either parenchymal necrosis or portal inflammation, and an elevation of conjugated bilirubin in the serum. In addition, Schaffner and Popper (6) have shown that ultrastructural alterations of the liver comprizing a widespread dilatation of the biliary canaliculi and distortion of the canalicular microvilli are invariably associated with the intrahepatic cholestasis.
Several authors have reported experimental studies in relation to the cholestatic effect of steroids. Schaffner and Popper (6) have demonstrated the occurence of canalicular dilatation in the liver of rats following administration of norethandrolone. Retardation of bromosulphalein excretion is known to occur in animals treated with methyltestosterone and norethandrolone (7-9). However, the experimental model with definite manifestations of intrahepatic bile-stasis such as conjugated hyperbilirubinemia or canalicular bile-plugs has not been established.
In the course of studying the acute toxicity of norethisterone, 17α-ethinyl-19-nortestosterone, we found a consistent appearance of jaundice in DS mice following administration of a large amount of norethisterone as well as other C17 α-alkyl or alkynyl substituted steroids. This experiment attempted to evaluate the pathological entities of the norethisterone-induced jaundice in mice in comparison with the intrahepatic cholestasis in men caused by various steriod drugs.
