Induction of Hepatic Mitochondrial Glycerophosphate Dehydrogenase in Rats by Dehydroepiandrosterone

Abstract

Feeding the thermogenic steroid, 5-androsten-3β-o1-17-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 (NADI⁺-linked) dehy-drogenases 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-3β, 17β-diol and 5-androsten-3β-o1-7, 17-dione were as effective as DHEA in enhancing the liver mitochondrial glycero-phosphate 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.