PMID: 8943797Sep 1, 1996Paper

Role of metabolism in the activation of dehydroepiandrosterone as a peroxisome proliferator

The Journal of Endocrinology
D J Waxman

Abstract

The adrenal steroid dehydroepiandrosterone (DHEA) stimulates a dramatic increase in both the size and the number of peroxisomes present in liver when given at pharmacological doses to rodents. Structurally diverse chemicals including many fatty acids, hypolipidemic drugs and other foreign chemicals, can also induce such a peroxisome proliferative response. This response is associated with a dramatic induction of perosisomal fatty acid beta-oxidation enzymes and microsomal cytochrome P450 4A fatty acid hydroxylases and, long-term, can lead to induction of hepatocellular carcinoma. This review examines the underlying mechanisms by which DHEA induces peroxisome proliferation and evaluates the possible role of peroxisome proliferator-activated receptor (PPAR) in this process. Like DHEA, the 17 beta-reduced metabolite 5-androstene-3 beta. 17 beta-diol (ADIOL) is an active peroxisome proliferator when administered in vivo, whereas androgenic and estrogenic metabolites of DHEA are inactive. In primary rat hepatocytes, however, DHEA and ADIOI are inactive as inducers of P450 4A and peroxisomal enzymes unless first metabolized by steroid sulfotransferase to the 3 beta-sulfates, DHEA-S and ADIOL-S. Investigations as to whether DHEA utili...Continue Reading

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