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.
Department of Pathology, Northwestern University Medical School, Chicago, IL 60611.
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MS
Rao
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Ide
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Alvares
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Subbarao
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Reddy
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Hechter
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Yeldandi
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000187:drug effects / Q000235:genetics; D000735:Androstenedione / Q000494:pharmacology; D000738:Androsterone / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D004746:Enoyl-CoA Hydratase / Q000187:drug effects / Q000235:genetics; D004958:Estradiol / Q000494:pharmacology; D004970:Estrone / Q000494:pharmacology; D005043:Etiocholanolone / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344
D012333:RNA, Messenger; D004970:Estrone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D004958:Estradiol; D005043:Etiocholanolone; D000738:Androsterone; D015094:3-Hydroxyacyl CoA Dehydrogenases; D004746:Enoyl-CoA Hydratase