Reduced hepatic content of dehydroepiandrosterone sulphotransferase in chronic liver diseases.
OBJECTIVE
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 reduced in cytosol of liver from miscellaneous patients with chronic liver disease. The aim of this study was to investigate the cause of diminished sulphotransferase activity in order to further our understanding of whether a reduction in the ability to sulphate potentially hepatotoxic bile acids might play a role in the aetiology of primary cholestatic liver disease.


METHODS
We quantified DHEA ST in human liver cytosol from groups of patients with chronic liver diseases and normal subjects using a semiquantitative sodium dodecyl sulphate/polyacrylamide gel electrophoresis (SDS-PAGE)/ immunoblotting method, and an enzyme-linked immunosorbent assay (ELISA). We determined DHEA ST enzyme activity and correlated it with its immunoreactive concentration in 87 samples of human liver tissue.


RESULTS
DHEA ST activity and concentration were significantly reduced in primary biliary cirrhosis, primary sclerosing cholangitis, chronic active hepatitis and alcoholic cirrhosis but not in cryptogenic cirrhosis when compared to normal liver. There were no significant differences among disease groups. In all groups enzyme activity and cellular concentration correlated, suggesting that no aberrant non-functional enzyme was produced.


CONCLUSIONS
These results confirm that DHEA 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.
Elekima
O T
OT
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, UK.
Mills
C O
CO
Ahmad
A
A
Skinner
G R
GR
Ramsden
D B
DB
Bown
J
J
Young
T W
TW
Elias
E
E
D000328:Adult; D000818:Animals; D015153:Blotting, Western; D002908:Chronic Disease; D003600:Cytosol / Q000201:enzymology; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008107:Liver Diseases / Q000201:enzymology* / Q000473:pathology; D008875:Middle Aged; D011817:Rabbits; D015238:Sulfotransferases / Q000378:metabolism*
D015238:Sulfotransferases; C019998:dehydroepiandrosterone sulfotransferase