COMPARATIVE EFFECTS OF DEHYDROEPIANDROSTERONE AND RELATED STEROIDS ONPEROXISOME PROLIFERATION IN RAT-LIVER

Dehydroepiandrosterone (DHEA) is known to induce peroxisome proliferat ion and peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenas e (PBE) mRNA in the rat liver. We have compared the effects of 6 inter mediate metabolites of DHEA on the induction of peroxisome proliferati on and PBE mRNA. Administration of epiandrosterone, etiocholanolone, a ndrostenedione, estrone or estradiol for 2 weeks in the diet at 0.45% concentration to adult male F-344 rats failed to induce significant in creases in peroxisome proliferation and PBE mRNA when compared to the parent compound DHEA. Dietary administration of 5-androstene-3beta,17b eta-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 DHE A or possibly another yet to be identified metabolite might be respons ible for peroxisome proliferation.