Relationship between the increase in liver nuclear triiodothyronine-receptor sites and malic enzyme activation by dexamethasone.
Previous works have indicated that a glucocorticoid excess results in an increase in the maximal binding capacity of nuclear T3-receptors (MBC) and in the activity of cytosolic malic enzyme (ME) in the liver of the rat. In this paper, studies were undertaken to evaluate the degree of dependency between the changes in the nuclear T3-receptor number and the induction of a specific metabolic response of T3 evaluated by the activity of ME. The injection of graded daily doses of dexamethasone to adrenalectomized animals (Ax) induced a dose-related increase in MBC and ME activity, and their maximal values were reached with the same dose of dexamethasone. The time-related changes in MBC and ME after the administration of a daily dose of dexamethasone indicated that both parameters followed a progressive-time increase which was evident 24 h after the glucocorticoid until the highest level's were reached. MBC and ME were measured in thyroidectomized (Tx) rats and Tx plus Ax rats injected with dexamethasone (Tx + Ax + D). MBC increased significantly in Ax animals treated with dexamethasone (Ax + D) and in Tx + Ax + D compared with the Tx and control groups. ME activity was very low in Tx animals and dexamethasone injection to Tx + Ax animals did not increase the enzyme activity as occurred in the Ax group where the serum T3 level was in the normal range. These data indicate that the increase in ME activity by dexamethasone administration was associated to a simultaneous increase in the number of liver nuclear T3-receptors. Dexamethasone injected to hypothyroid animals failed to induce a ME activation as it was found in animals with normal T3 levels, suggesting a T3-mediated action of dexamethasone on ME activity by modification of the nuclear T3-receptor number.
D000818:Animals; D001665:Binding Sites; D003907:Dexamethasone / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D008099:Liver / Q000378:metabolism*; D008291:Malate Dehydrogenase / Q000378:metabolism*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011988:Receptors, Thyroid Hormone / Q000032:analysis / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism*
D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D003907:Dexamethasone; D008291:Malate Dehydrogenase