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To elucidate the molecular basis of the induction of peroxisomal enzymes, transcriptional regulation of the acyl-CoA oxidase (AOX) gene by dehydroepiandrosterone sulfate (DHEAS) was examined using primary cultures of rat hepatocytes. Incubation of the hepatocytes with 0.1 mM DHEAS resulted in a progressive increase in the cellular AOX mRNA level, which after 24 h reached a 5.6-fold higher level than that in the control cells treated with vehicle alone. However, this mRNA induction was completely inhibited by alpha-amanitin, an RNA polymerase II inhibitor. When examined by the nuclear run-on transcription assay, the rate of de novo synthesis of AOX mRNA was 3- to 4-fold higher in the hepatocytes exposed to DHEAS than in the control cells, even after 3h. These results indicate that DHEAS acts directly on hepatocytes to activate the transcription of the AOX gene, which leads to the marked induction of AOX in the cell.

Transcriptional Induction of Acyl-CoA Oxidase by Dehydroepiandrosterone Sulfate in Cultured Rat Hepatocytes.