Plasma adrenocorticotropin is more sensitive than transcortin production or thymus weight to inhibition by corticosterone in rats.
After adrenalectomy, ACTH, corticosterone-binding globulin (CBG), and thymus wet weight increase in rats as a consequence of the removal of corticosterone (B) and decrease again in response to replacement with glucocorticoids. We have studied the effect of replacing adrenalectomized male rats with a variety of different concentrations of B. Plasma concentrations of ACTH and CBG and thymus wet weights were related to the measured concentration of free ultrafilterable B in plasma. In other experiments, the clearance of [125I]CBG was determined in adrenalectomized rats with and without B replacement, and the time required for the changes in plasma CBG concentrations after removal and/or replacement of B in adrenalectomized rats was determined. Five to 7 days after adrenalectomy and institution of a relatively constant B replacement signal, plasma CBG concentrations were highly correlated with circulating B concentrations (r2 = 0.745; P less than 0.001). The effect of B was on the CBG production rate, since clearance did not change. Because CBG concentrations decrease as total B concentrations increase, there is an amplification of free B concentrations with increasing total B. The relationships of plasma ACTH and CBG and thymus wet weight to circulating free B levels showed that 50% inhibition of ACTH was achieved at a free B concentration of 0.8 +/- 0.05 nM, whereas 50% inhibition of CBG and thymus wet weight were achieved at free B concentrations of 4.6 +/- 0.9 and 4.4 +/- 0.6 nM, respectively. These inhibition values correlate well with the known Kd values for the high affinity type I B receptor (0.5 nM) and for the lower affinity type II glucocorticoid receptor (2.5-5 nM), respectively, suggesting that ACTH secretion, CBG production, and thymus wet weight are regulated by the association of B with these receptor types.