Induction of hepatic mitochondrial glycerophosphate dehydrogenase in rats by dehydroepiandrosterone.
Feeding the thermogenic steroid, 5-androsten-3 beta-ol-17-one (dehydroepiandrosterone, DHEA) in the diet of rats induced the synthesis of liver mitochondrial sn-glycerol 3-phosphate dehydrogenase to levels three to five times that of control rats within 7 days. The previously reported enhancement of liver cytosolic malic enzyme was confirmed. The induction of both enzymes was detectable at 0.01% DHEA in the diet, reached plateau stimulation at 0.1 to 0.2%, and was completely blocked by simultaneous treatment with actinomycin D. Feeding DHEA caused smaller, but statistically significant increases of liver cytosolic lactate, sn-glycerol 3-phosphate, and isocitrate (NADP(+)-linked) dehydrogenases but not of malate or glucose 6-phosphate dehydrogenases. The capability of DHEA to enhance mitochondrial glycerophosphate dehydrogenase and malic enzyme was influenced by the thyroid status of the rats; was smallest in thyroidectomized rats and highest in rats treated with triiodothyronine. 5-Androsten-3 beta,17 beta-diol and 5-androsten-3 beta-ol-7,17-dione were as effective as DHEA in enhancing the liver mitochondrial glycerophosphate dehydrogenase and malic enzyme. Administering compounds that induce the formation of cytochrome P450 enzymes enhanced liver malic enzyme activity but not that of mitochondrial glycerophosphate dehydrogenase. Arochlor 1254 and 3-methylcholanthrene also increased the response of malic enzyme to DHEA feeding.
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Department of Biochemistry, University of Wisconsin, Madison 53705.
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D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004032:Diet; D004790:Enzyme Induction; D005260:Female; D005993:Glycerolphosphate Dehydrogenase / Q000096:biosynthesis* / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013379:Substrate Specificity
D003687:Dehydroepiandrosterone; D003577:Cytochrome P-450 Enzyme System; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase