Distinction between binding of [3H]triamcinolone acetonide to a ligand binding domain on the glucocorticoid receptor complex in cytosol fractions of brain and liver from the rat with intact adrenals.

Abstract

Binding of [3H]triamcinolone acetonide (TA) was examined to evaluate possible differences in biochemical and pharmacological profiles of a ligand binding domain on the naive glucocorticoid (GC) receptor complex between cytosol fractions of brain and liver obtained from the rat with intact adrenals. Unlabeled TA was 3-times less potent in displacing [3H]TA binding at equilibrium in the presence of Na2MoO4 at 2 degrees C in brain than in liver, while dexamethasone was more than 15-times more potent in displacing brain binding than liver binding. Both progesterone and aldosterone caused more than 20-times more potent displacement of [3H]TA binding in brain than in liver. However, zinc ions were effective in similarly inhibiting binding at equilibrium via lowering the affinity without affecting the density. In contrast to these experiments done at 2 degrees C, the addition of Na2MoO4 potentiated binding in brain and liver in a transient manner at 30 degrees C. Prolongation of incubation period from 30 min to 5 h induced a rightward shift of concentration-response curves of Na2MoO4 for [3H]TA binding at 30 degrees C in brain and liver in an irreversible fashion. The potentiation by Na2MoO4 was prevented by the addition of leupeptin but not 5 other protease inhibitors in brain cytosol fractions. Ion exchange chromatography revealed that elution profiles were entirely different from each other for [3H]TA binding between brain and liver cytosol fractions. These results suggest that GC receptors may respond to a variety of signals mediated by different steroid hormones through broader pharmacological spectrum of the ligand binding domain in brain than in liver.