Dehydroepiandrosterone-Induced Peroxisome Proliferation in the Rat Liver

We have investigated the effect of dehydroepiandrosterone (DHEA), a naturally occurring steroid hormone, on hepatic peroxisomes in the rat. Dietary administration of DHEA at a concentration of 0.45% for 2 weeks resulted in a 200% increase in the liver weight and a more than 5.0-fold increase in the volume density of peroxisomes. SDS-polyacrylamide gel electrophoresis of the postnuclear fraction of livers showed a marked increase in the 80,000-molecular weight polypeptide. Northern blot analysis of total RNA showed 2- and 12-fold increases, respectively, in the levels of catalase and peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme (PBE) mRNA. Administration of a single large dose of DHEA led to a 10- to 40-fold increase in PBE mRNA levels by 24 h. These changes are qualitatively similar to those caused by a variety of structurally different peroxisome proliferators.