Impact of dehydroepiandrosterone on hepatocarcinogenesis in the rat (Review).
The role of dehydroepiandrosterone (DHEA) in liver carcinogenesis remains a topic of widespread research. Studies in rats suggest a hepatocarcinogenetic effect of DHEA. The incidence of DHEA-induced hepatocellular neoplasms depends on the rat strain, the gender, and the dose and duration of the treatment. Gender specific differences observed regarding the incidence of DHEA-induced hepatocellular neoplasms suggest a hormonal impact of the treatment. Studies in rats, which initially had been treated with chemical carcinogens and subsequently underwent a DHEA administration with various doses, disclose both, DHEA associated hepatic tumour promotion and hepatic tumour inhibition. These findings depend on the type, dose and duration of the initial intoxication and of the DHEA treatment. DHEA administration to rats also induces multiple profound alterations of the liver metabolism. Metabolism during DHEA treatment is characterized by an overall increase in energy expenditure. Lipid and glucose metabolism of the liver is changed profoundly switching from an anabolic to a catabolic state. This energy waste may be related to the inhibitory action of DHEA on tumour growth. Tumour enhancement is due to promotion of a specific type of preneoplastic liver lesions with a basophilic phenotype. This review summarizes the current knowledge on DHEA effects on the liver and discusses molecular and functional aspects that may explain the paradoxical effects of DHEA regarding hepatocarcinogenesis.
Mayer
Doris
D
Research Group Hormones and Signal Transduction, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. d.mayer@dkfz-heidelberg.de
Forstner
Klaus
K
D000818:Animals; D019070:Cell Lineage; D003687:Dehydroepiandrosterone / Q000633:toxicity*; D004734:Energy Metabolism / Q000187:drug effects; D006801:Humans; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008830:Microbodies / Q000187:drug effects / Q000473:pathology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D003687:Dehydroepiandrosterone