THE EFFECTS OF THE ERGOSTEROID 7-OXO-DEHYDROEPIANDROSTERONE ON MITOCHONDRIAL-MEMBRANE POTENTIAL - POSSIBLE RELATIONSHIP TO THERMOGENESIS

Administered 3 beta-hydroxyandrost-5-ene-7,17-dione (7-oxo-DHEA) is mo re effective than 3 beta-hydroxyandrost-5-en-7-one (DHEA) as an induce r of liver mitochondrial sn-glycerol-3-phosphate dehydrogenase and cyt osolic malic enzyme in rats. Like DHEA, the 7-oxo metabolite enhances Liver catalase, fatty acylCoA oxidase, cytosolic sn-glycerol-3-phospha te dehydrogenase, mitochondrial substrate oxidation rate, and the reco nstructed sn-glycerol 3-phosphate shuttle. The mitochondrial adenine n ucleotide carrier is diminished by thyroidectomy and is restored to no rmal activity by administering 7-oxo DHEA. The relationship between re spiratory rate and proton motive force across the mitochondrial membra ne was measured in the nonphosphorylating state. When treated with inc reasing concentrations of respiratory inhibitors liver mitochondria fr om rats treated with 7-oxo-DHEA or thyroid hormones show a more rapid decline of membrane potential than do normal liver mitochondria. Thus 7-oxo-DHEA induces an increased proton leak or slip as has been report ed for the thyroid hormone by M. D. Brand [(1990) Biochem. Biophys. Ac ta 1018, 128-133]. This process may contribute to the enhanced thermog enesis caused by ergosteroids as well as by thyroid hormones. (C) 1997 Academic Press.