The effects of the ergosteroid 7-oxo-dehydroepiandrosterone on mitochondrial membrane potential: possible relationship to thermogenesis.
Bobyleva V, Bellei M, Kneer N, Lardy H.
Dipartimento di Scienze Biomediche, Universita di Modena, Italy.
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.
Relationship of dehydroepiandrosterone and its 7-hydroxylated metabolites to thyroid parameters and sex hormone-binding globulin (SHBG) in healthy subjects.
Hampl R, Hill M, Bilek R, Starka L.
Institute of Endocrinology, Prague, Czech Republic.
[email protected]
The concentrations of four immunomodulatory steroids, namely dehydroepiandrosterone (DHEA), its sulfate and its 7-hydroxylated metabolites, and sex hormone-binding globulin (SHBG) and major laboratory parameters of thyroid function were determined in sera from 104 healthy females and 48 males, screened for iodine deficiency in one region of the Czech Republic. The mutual relationships of the laboratory parameters were investigated by using four statistical approaches: correlation analysis, principal component analysis, canonical correlation and linear model relationship. In addition to expected correlations among thyroid parameters and substrate-product relationships among the steroids, several new relationships were revealed: The only thyroid parameter tightly correlating with SHBG was free triiodothyronine. The latter hormone was also associated with one of the 7-OH-DHEA epimers, namely with 7beta-OH-DHEA. Thyroid hormones are known to possess thermogenic properties, as does another 7-oxygenated DHEA metabolite, 7-oxo-DHEA, the major metabolite of which is 7beta-OH-DHEA. It may indicate a link between the two thermogenic factors. The results should serve for further investigation of changes in the thyroid hormone concentrations, together with SHBG and dehydroepiandrosterone metabolites, under various pathological situations.