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 more effective than 3 beta-hydroxyandrost-5-en-7-one (DHEA) as an inducer of liver mitochondrial sn-glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme in rats. Like DHEA, the 7-oxo metabolite enhances liver catalase, fatty acylCoA oxidase, cytosolic sn-glycerol-3-phosphate dehydrogenase, mitochondrial substrate oxidation rate, and the reconstructed sn-glycerol 3-phosphate shuttle. The mitochondrial adenine nucleotide carrier is diminished by thyroidectomy and is restored to normal activity by administering 7-oxo-DHEA. The relationship between respiratory rate and proton motive force across the mitochondrial membrane was measured in the nonphosphorylating state. When treated with increasing concentrations of respiratory inhibitors liver mitochondria from 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 reported for the thyroid hormone by M.D. Brand [(1990) Biochem. Biophys. Acta 1018, 128-133]. This process may contribute to the enhanced thermogenesis caused by ergosteroids as well as by thyroid hormones.