The effect of dehydroepiandrosterone on liver metabolites.
Liver metabolites and in vitro enzyme activities were measured in Sprague-Dawley rats pair-fed the standard NIH diet with or without 0.6% (wt/wt) dehydroepiandrosterone (DHEA) for 16 d. Absorption of DHEA from the gut was confirmed by a 300-fold increase in urine 17-ketosteroids in DHEA-treated animals. Of the liver metabolites measured only 6-phosphogluconate was significantly changed, increasing by less than a factor of two in the DHEA-treated animals, 38.7 +/- 2.2 nmol/g, above the value in the pair-fed controls, 22.5 +/- 2.5 nmol/g. Contrary to the in vitro findings that DHEA inhibits glucose-6-phosphate dehydrogenase (EC 1.1.1.49), thus leading to the hypothesis that DHEA inhibits fat synthesis by diminishing the availability of NADPH, the [NADP+]/[NADPH] ratios calculated from the 6-phosphogluconate dehydrogenase (EC 1.1.1.44), isocitrate dehydrogenase (EC 1.1.1.42) and malic enzyme (EC 1.1.1.40) redox couples were no more oxidized in the DHEA-treated animals than in the control animals. Malic enzyme and isocitrate dehydrogenase activities were 620 and 25% higher in DHEA-treated animals than in pair-fed controls. There was no change in the measured activity of glucose-6-phosphate dehydrogenase or 6-phosphogluconate dehydrogenase. These data give no support to the hypothesis that administration of DHEA per os results in decreased cytoplasmic NADPH in liver.
D015068:17-Ketosteroids / Q000652:urine; D000818:Animals; D001835:Body Weight; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004032:Diet; D005502:Food; D005942:Gluconates / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D009249:NADP / Q000378:metabolism; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D015068:17-Ketosteroids; D005942:Gluconates; D003687:Dehydroepiandrosterone; D009249:NADP; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; C008884:6-phosphogluconic acid