Antiglucocorticoid action of dehydroepiandrosterone in young obese Zucker rats.
Dehydroepiandrosterone (DHEA) reduces weight gain in the hypercorticosteronemic Zucker fatty rat, an animal model of genetic obesity. However, the mechanism of action of DHEA is still unclear. We propose that DHEA acts as an antiglucocorticoid in the Zucker fatty rat. To test this hypothesis we examined DHEA's ability to block the activation of the glucocorticoid-inducible enzymes tyrosine aminotransferase (TAT) and ornithine decarboxylase (ODC) by dexamethasone (i.p. 5 micrograms/100 g body weight) in hepatic tissue of 6-10 week old Zucker rats. Injections of DMSO, the vehicle, served as a control. DHEA alone did not affect TAT, but when DHEA (500 micrograms/100 g b.w.) was administered simultaneously with dexamethasone, activation did not occur. Similar results were seen using a second tissue (kidney). We conclude that DHEA can act acutely as an antiglucocorticoid in the young obese Zucker rat and hypothesize that its chronic anti-obesity effect may reflect, at least in part, a chronic antiglucocorticoid activity.
Department of Physiology, Louisiana State University Medical Center, New Orleans 70119.
B E
BE
Wright
J R
JR
Porter
E S
ES
Browne
F
F
Svec
D000704:Analysis of Variance; D000818:Animals; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000037:antagonists & inhibitors*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D009765:Obesity / Q000201:enzymology*; D009955:Ornithine Decarboxylase / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D011924:Rats, Zucker; D014444:Tyrosine Transaminase / Q000187:drug effects
D005938:Glucocorticoids; D003687:Dehydroepiandrosterone; D014444:Tyrosine Transaminase; D009955:Ornithine Decarboxylase