Comparative effects of dehydroepiandrosterone and related steroids on peroxisome proliferation in rat liver

Dehydroepiandrosterone (DHEA) is known to induce peroxisome proliferation and peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (PBE) mRNA in the rat liver. We have compared the effects of 6 intermediate metabolites of DHEA on the induction of peroxisome proliferation and PBE mRNA. Administration of epiandrosterone, etiocholanolone, androstenedione, estrone or estradiol for 2 weeks in the diet at 0.45% concentration to adult male F-344 rats failed to induce significant increases in peroxisome proliferation and PBE mRNA when compared to the parent compound DHEA. Dietary administration of 5-androstene-3 beta,17 beta-diol (ADIOL) for 2 weeks at 0.45% concentration caused an increase in PBE mRNA and peroxisome proliferation but to a lesser extent than DHEA. Following a single intragastric dose of DHEA an increase in PBE mRNA level was observed in the liver at 1 hr and continued to 16 hrs., but not with its metabolites. These results strongly suggest that DHEA or possibly another yet to be identified metabolite might be responsible for peroxisome proliferation.