The effect of previous stimulation of the adrenal cortex by adrenocorticotrophin on the function of the pituitary-adrenocortical axis in response to stress.

1. There appear to be at least two peripheral regulators affecting normal physiological adrenal function during repeated stimulation with adrenocorticotrophin (ACTH).2. There is a tachyphylaxis to ACTH if the stimulation of the adrenal gland is frequent. This may be due to alteration or saturation of the trapping mechanism for acceptance of ACTH by the tissue. There also may be inhibitors at the adrenal level. The results obtained could also be explained on the basis of end product inhibition by corticosterone on the process of synthesis or by the presence of a destructive enzyme for ACTH.3. If the amounts of ACTH released or injected are sufficiently great the gland is capable of synthesizing more steroid but adrenocortical dynamics do not allow an immediate release of the steroid into the peripheral circulation. Thereby high levels of steroid in the plasma are maintained for longer periods rather than increased.