Dehydroepiandrosterone regulation of the hepatic glucocorticoid receptor in the Zucker rat. The obesity research program.
Dehydroepiandrosterone (DHEA) decreases the activity of hepatic tyrosine aminotransferase (TAT), a glucocorticoid-inducible enzyme, in the obese, hypercorticosteronemic Zucker rat. To investigate the mechanism of this antiglucocorticoid action, the effect of exogenous DHEA on hepatic glucocorticoid receptor (GC) number and affinity was quantitated. Food supplementation with DHEA (0.6% w/w) for 1 or 7 days had no effect on either receptor number or affinity in obese Zucker rats. After 28 days, however, DHEA treatment resulted in a nearly 40% decrease in cytosolic hepatic receptor content (Bmax; fmol/mg cytosolic protein) without any change in affinity (Kd) in both lean and obese rats. DHEA treatment for 28 days also resulted in an increased liver size and cytosolic protein content. When the hepatic GC receptor content was normalized based on the change in liver size and protein content, the apparent number of GC binding sites per liver was not affected by DHEA treatment. This observation suggests that DHEA's effect on GC receptor content may not be a specific action and that downregulation of the GC receptor is not the mechanism of DHEA action on GC induced TAT activity. This is supported by the effect of DHEA on obese rat TAT activity in the same experiment where the greatest inhibition occurred after only 1 day of treatment. From these experiments it is concluded that although long-term DHEA treatment may decrease the relative concentration of GC receptors in rat liver, this change is not the mechanism through which DHEA mediates its acute antiglucocorticoid action.
Browne
E S
ES
Department of Medicine, Louisiana State University Medical Center, New Orleans.
Porter
J R
JR
Correa
G
G
Abadie
J
J
Svec
F
F
D000818:Animals; D001667:Binding, Competitive; D003687:Dehydroepiandrosterone / Q000502:physiology*; D005260:Female; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D011924:Rats, Zucker; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D014444:Tyrosine Transaminase / Q000378:metabolism
D011965:Receptors, Glucocorticoid; D003687:Dehydroepiandrosterone; D014444:Tyrosine Transaminase