Reduced hepatic content of dehydroepiandrosterone sulphotransferase in chronic liver diseases

Aims/Background: Dehydroepiandrosterone sulphotransferase (DHEA ST) is the enzyme responsible for sulphation of lithocholic acid and other potentially hepatotoxic steroids. We have previously shown that DHEA ST activity is re duced in cytosol of liver from miscellaneous patients with chronic liver di sease. The aim of this study was to investigate the cause of diminished sul photransferase activity in order to further our understanding of whether a reduction in the ability to sulphate potentially hepatotoxic bile acids mig ht play a role in the aetiology of primary cholestatic liver disease. Metho ds: We quantified DHEA ST in human liver cytosol from groups of patients wi th chronic liver diseases and normal subjects using a semiquantitative sodi um dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE)/immunoblo tting method, and an enzyme-linked immunosorbent assay (ELISA). We determin ed DHEA ST enzyme activity and correlated it with its immunoreactive concen tration in 57 samples of human liver tissue. Results: DHEA ST activity and concentration were significantly reduced in primary biliary cirrhosis, prim ary sclerosing cholangitis, chronic active hepatitis and alcoholic cirrhosi s but not in cryptogenic cirrhosis when compared to normal liver. There wer e no significant differences among disease groups. In all groups enzyme act ivity and cellular concentration correlated, suggesting that no aberrant no nfunctional enzyme was produced. Conclusion: These results confirm that DHE A ST activity is diminished in liver disease and that the reduction is due to diminished enzyme presence. Further studies are required to show whether the reduction has any pathogenetic significance or is merely a consequence of disease.