Liver cirrhosis and oestrogen metabolism--perfusion studies with cirrhotic rat livers

1. Radioactive oestrone and oestradiol-17 beta were perfused through normal and cirrhotic livers of rats. Liver cirrhosis had been induced by a combined application of carbon tetrachloride and azathioprine. 2. The hepatic uptake of both oestrogens by cirrhotic livers was reduced; the uptake of oestrone was more affected than that of oestradiol-17 beta. 3. The pattern of oestrogen metabolites indicated a reduction of the sulphotransferase activity in cirrhotic livers. The activity of other enzymes of oestrogen metabolism were similar in normal and cirrhotic livers. 4. The amount of oestrogen glucuronides excreted into the bile was significantly less in cirrhotic livers although the bile volume was larger in cirrhotic than normal livers. 5. The release of oestrogen metabolites into the circulating medium was considerably higher during perfusion of cirrhotic livers. From the findings presented here it is concluded that the turnover of oestrogens is slower in cirrhotic than in normal livers. Moreover, it may be speculated that the distribution volume of the oestrogen metabolites is smaller in rats with liver cirrhosis, due to a disturbed enterohepatic circulation. This results in higher oestrogen concentrations in extracellular fluids, thus supporting the concept of hyper-oestrogenism in liver cirrhosis.