Selective alterations in hepatic nuclear T3-receptors and enzyme responses by glucocorticoid deficit or excess.
Glucocorticoid deficit in rats induced by adrenalectomy for a 10-day period resulted in an increase in the apparent association constant (Ka) of the liver nuclear T3-receptor while maximal binding capacity (MBC) remained unaltered compared to the intact (sham-operated) animals and to adrenalectomy plus dexamethasone (Sx + D) animals. In addition, a significant increase in the basal activity of liver mitochondrial alpha-glycerophosphate dehydrogenase (alpha-GPD) was observed, while cytosolic malic enzyme (ME) activity was not modified in this situation. Dexamethasone injection (5 mg/kg/day for 4-5 days) to previously adrenalectomized animals (Sx + D) induced a significant increase in MBC of nuclear T3-receptors. On the other hand, Ka value and alpha-GPD activity were restored to the values found in the control group. However, basal activity of ME as well as the response of this enzyme to a saturating dose of T3 was substantially increased by dexamethasone treatment. A non-specific in vitro effect of dexamethasone on MBC and ME was excluded as these parameters were not modified when dexamethasone was added immediately before the in vitro assays. The present study indicates that glucocorticoid deficit or excess is able to induce changes at the level of the nuclear T3-receptor site. The increase in the activity of cytolic ME induced by dexamethasone injection was associated with a simultaneous increase in the T3-receptor capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
D000315:Adrenalectomy; D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D011956:Receptors, Cell Surface; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D003907:Dexamethasone; D008291:Malate Dehydrogenase; D013974:Thyroxine