Abstract
Adrenal steroid (AS) receptors differ from other steroid receptors in the inability of the activated form of the cytosolic receptor to exchange ligand in an in vitro binding assay. We extended this finding by demonstrating that AS receptors extracted from isolated brain nuclei also failed to exchange ligand. Taking advantage of this unique feature of AS receptors, we measured type I and type II AS binding level in rats with varying amounts of endogenous glucocorticoids or exogenous dexamethasone (DEX). We estimated the degree of receptor occupation/ activation in various brain areas and the pituitary during basal glucocorticoid conditions and after acute stress. There was a variable proportion of type I receptors in the hippocampus which were unactivated during basal conditions (0–35%). The proportion of unactivated type I receptors increase (55–65%) after DEX treatment. The hippocampus was especially sensitive to the ability of low basal corticosterone (CORT) levels to activate both type I and type II receptors, whereas the pituitary was very insensitive, evidenced by a failure of acute stress levels of endogenous glucocorticoids to occupy/activate type II receptors in the pituitary. Comparison of estimates of the degree of in vivo hippocampal type I and type II receptor activation for the various treatment groups with estimates of in vitro type I and type II receptor occupation by steroid suggested that DEX was more efficient than CORT in producing or maintaining the activated form of the type II receptor in vivo, whereas CORT was more efficient than DEX in activating the type I receptor. These studies suggest that AS receptors in the brain, and especially the hippocampus, are more sensitive to circulating levels of glucocorticoids than the pituitary. There also may be a greater capacity for physiological variations in type I receptor occupation in vivo than had previously been suggested. Finally, discrepancies between CORT and DEX affinity in vitro for type I and type II sites and their in vivo potency may be accounted for by differences in the ability of these compounds to activate type I and type II AS receptors.
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