Corticosterone: narrow range required for normal body and thymus weight and ACTH

ACTH secretion appears to be under fairly tight negative feedback control by corticosteroids secreted from the adrenal cortex. In these studies we determined the circulating levels of a constant corticosterone signal that best restored body weight gain, thymus weight and ACTH levels to normal in bilaterally adrenalectomized rats given saline to drink. Young male rats were treated at the time of adrenalectomy with subcutaneously implanted pellets of wax or various ratios of corticosterone-cholesterol. Sham-adrenalectomized rats and adrenalectomized rats given corticosterone in the drinking fluid served as comparison groups. Rats were killed 3, 7, or 14 days after adrenalectomy. There was no difference in levels of plasma corticosterone in the morning and in the evening in pellet-implanted rats in contrast to the diurnal variation in the reference groups. Circulating corticosterone levels that best restored body weight, thymus weight, and resting and stress-induced ACTH levels to normal ranged between 4.5 and 7.4 micrograms/dl. Plasma corticosterone levels of 8-11 micrograms/dl were excessive and levels of 2-4 micrograms/dl were not adequate. We conclude that there is a very narrow range of plasma corticosterone compatible with normal growth rate, thymus mass and ACTH secretion. These results reveal the necessity for strict negative feedback regulation of ACTH secretion by corticosteroids.