Abstract

Adrenalectomy-induced increases in ACTH secretion in rats are returned to normal by an action of corticosterone on the brain, not on the pituitary. Five days after adrenalectomy with constant steroid replacement, the concentration of free corticosterone in plasma which reduces plasma ACTH by 50% is approximately 0.8 nM. By contrast, the concentration of free plasma corticosterone required for 50% reduction of thymus wet weight or plasma transcortin concentration (both targets for glucocorticoid action) is about 4.5 nM. These results suggested that the inhibition of ACTH by corticosterone might be mediated by association of the steroid with high affinity, type I corticosteroid receptors, whereas the inhibition of thymus weight and transcortin might be mediated by association of the steroid with lower affinity, type II receptors. The results of studies comparing the ability of corticosterone, dexamethasone and aldosterone to inhibit adrenalectomy-induced ACTH secretion support the hypothesis that basal ACTH secretion in rats is mediated by association of corticosterone with type I receptors.