Short-term effects of dehydroepiandrosterone treatment in rats on mitochondrial respiration.
Administration of dehydroepiandrosterone (DHEA) to rats results in alterations in liver and serum factors. This study was undertaken to determine the earliest metabolic change(s) associated with DHEA treatment. Serum cholesterol, triacylglycerol, glucose, insulin, glucagon, thyroid hormones and hepatic glucose-6-phosphate dehydrogenase activity were, in general, unaltered in obese Zucker rats after 7 d and 24, 12 and 3 h of DHEA treatment. Malic enzyme, long-chain fatty acyl-coenzyme A hydrolase and catalase activities and peroxisomal beta-oxidation rates were elevated after 7 d and 24 h in DHEA treatment, but not after 12 h. Mitochondrial beta-oxidation was not altered. Hepatic mitochondrial state 3 respiration per g liver with glutamate-malate was elevated after 7 d and 24, 12 and 3 h in DHEA-treated rats and was elevated per mg protein except after 7 d. Succinate-supported state 3 respiration per g liver was also elevated after 7 d and 24 and 12 h of DHEA treatment. Mitochondria from rats treated for 7 d had lower levels of cardiolipin and phosphatidylethanolamine and an increase in phosphatidylcholine. Changes in fatty acid composition of these phospholipids occurred after 7 d and 24 h of DHEA treatment. In an additional study, rats were treated with DHEA or DHEA plus ethidium bromide for 3 d. Ethidium bromide inhibited the increase in mitochondrial protein and respiration associated with DHEA treatment. These findings indicate that mitochondrial respiration is the earliest factor affected by DHEA and may be associated with protein synthesis.
Mohan
P F
PF
Hormel Institute, University of Minnesota, Austin 55912.
Cleary
M P
MP
D000214:Acyl Coenzyme A / Q000032:analysis; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002374:Catalase / Q000032:analysis; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D004996:Ethidium / Q000494:pharmacology; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000032:analysis; D008099:Liver / Q000201:enzymology; D008291:Malate Dehydrogenase / Q000032:analysis; D008830:Microbodies / Q000187:drug effects / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D011924:Rats, Zucker
D000214:Acyl Coenzyme A; D003687:Dehydroepiandrosterone; D008291:Malate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D004996:Ethidium