Dehydroepiandrosterone-induced peroxisome proliferation in the rat: evaluation of sex differences.
Dehydroepiandrosterone (DHEA) is a newly identified peroxisome proliferator that causes hepatomegaly, peroxisome proliferation, and induction of peroxisome-associated enzymes in rats and mice, and hepatocellular carcinomas in rats. In the present study, we have systematically analyzed sex differences and the effect of castration on DHEA-induced peroxisome proliferation in male and female rats, since no information is available on this subject. DHEA was fed in diet at a concentration of 0.45% for 2 weeks and livers were analyzed for hepatomegaly, peroxisome volume density, peroxisome proliferator associated Mr 80,000 polypeptide (PPA-80), and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (PBE) mRNA. Both intact and castrated rats showed similar response to DHEA characterized by increased peroxisome volume density, PBE mRNA, and PPA-80. Significant difference was observed in the liver weights between castrated and intact animals in both the sexes. Castrated rats that received DHEA had 20%-30% more liver weight than DHEA-administered intact rats. These results clearly indicate that peroxisome proliferative effect of DHEA is not influenced by sex hormones and it is equally potent in both males and females.
Rao
M S
MS
Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611.
Reid
B
B
Ide
H
H
Subbarao
V
V
Reddy
J K
JK
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002369:Castration; D002455:Cell Division / Q000187:drug effects; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004746:Enoyl-CoA Hydratase / Q000235:genetics; D005260:Female; D008297:Male; D008830:Microbodies / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
D012333:RNA, Messenger; D003687:Dehydroepiandrosterone; D004746:Enoyl-CoA Hydratase