Ergosteroids: induction of thermogenic enzymes in liver of rats treated with steroids derived from dehydroepiandrosterone.
Dehydroepiandrosterone (DHEA), an intermediate in the biosynthesis of testosterone and estrogens, exerts several physiological effects not involving the sex hormones. When fed to rats it induces the thermogenic enzymes mitochondrial sn-glycerol-3-phosphate dehydrogenase and cytosolic malic enzyme in their livers. Animals and humans, and their excised tissues, are known to hydroxylate DHEA at several positions and to interconvert 7 alpha-hydroxy-DHEA, 7 beta-hydroxy-DHEA, 7-oxo-DHEA, and the corresponding derivatives of androst-5-enediol. We report here that these 7-oxygenated derivatives are active inducers of these thermogenic enzymes in rats and that the 7-oxo derivatives are more active than the parent steroids. We postulate that the 7 alpha-hydroxy and 7-oxo derivatives are on a metabolic pathway from DHEA to more active steroid hormones. These 7-oxo steroids have potential as therapeutic agents because of their increased activity and because they are not convertible to either testosterone or estrogens.
Lardy
H
H
Institute for Enzyme Research, University of Wisconsin, Madison 53705, USA.
Partridge
B
B
Kneer
N
N
Wei
Y
Y
D000818:Animals; D001833:Body Temperature Regulation; D003600:Cytosol / Q000201:enzymology; D003687:Dehydroepiandrosterone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004032:Diet; D004790:Enzyme Induction / Q000187:drug effects; D005993:Glycerolphosphate Dehydrogenase / Q000096:biosynthesis*; D006358:Hot Temperature; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008291:Malate Dehydrogenase / Q000096:biosynthesis*; D008930:Mitochondria, Liver / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley
D003687:Dehydroepiandrosterone; D005993:Glycerolphosphate Dehydrogenase; D008291:Malate Dehydrogenase; C030574:malate dehydrogenase (decarboxylating)