Dehydroepiandrosterone increases in zone of glutamine synthetase-positive hepatocytes in female rat liver: A putative androgenic effect

The adrenal steroid dehydroepiandrosterone (DHEA) is a hepatocarcinogen and peroxisome proliferator in the rat, producing an increase in peroxisomes m ainly in perivenular parts of the liver lobule. Glutamine synthetase (GS) i s expressed exclusively in hepatocytes that directly surround the central t erminal vein in rat Liver. The GS-positive zone is wider in males than in f emales, covering about two to three cell layers in males and one to two cel l layers in females. Treatment of rats with DHEA at a concentation of 0.6% in the diet for 4, 20, 32, 70 and 84 weeks resulted in an enlargement of th e GS-positive zone in females, whereas no change was observed in males. In females treated for up to 32 weeks with DHEA, the relative mean width (RMW) of the GS-positive zone was as large as that observed in males. The increa se in the RMW was paralleled by an increase in the number of GS-positive he patocytes. Upon longer treatment, the width of GS expression decreased to t hat observed in untreated controls. The findings suggest an androgenic effe ct of DHEA. The areas of peroxisome proliferation, identified in haematoxyl in and eosin- and periodic acid-Schiff-stained sections, and GS expression were not identical. Furthermore, preneoplastic and neoplastic liver lesions induced by DHEA were all negative for GS, indicating that they do not deri ve from the perivenular cells which show the most pronounced peroxisomal pr oliferation.