[Quantitative analysis of characteristics of the negative feedback regulation of ACTH secretion under stress...

Quantitative characteristics and a plausible mechanism of rapid rate-sensitive feedback inhibition of the CRF-ACTH-corticoid system were studied using Nembutal-anesthetized rats. The plasma corticosterone levels were varied by continuous infusion of corticosterone through a lateral caudal vein. The response to an intravenous injection of histamine (as a stressor) was distinctly inhibited in two phases of the dynamics of plasma corticosterone; one in its rapidly increasing phase (rapid rate-sensitive feedback inhibition) and the other, two hours or more after a high plasma steroid level has been attained (late level-sensitive feedback inhibition). On the other hand, there was no such inhibition between these two phases. A quantitative approach made by repeated blood sampling from single rats revealed that the critical rate of elevation of plasma corticosterone at which the rate-sensitive feedback inhibition). On the other hand, there was no such inhibition between these two phases. A quantitative approach made by repeated blood sampling from single rats revealed that the critical rate of elevation of plasma corticosterone at which the rate-sensitive inhibition begins to obviously occur was 4-6 mug%/min. Even with increasing strength of stress, the absolute size of inhibition at a fixed rate of elevation in plasma corticosterone remained almost the same. The increase in the median eminence-CRF activity, known to occur after stress, was effectively suppressed during the operation of rapid feedback inhibition. In addition, in brain noradrenaline-depleted rats, the rapid component in the feedback inhibition was thoroughly abolished, leaving the late component intact, while the opposite way in sorotonin-reduced rats. This finding suggests an involvement of brain biogenic amines in the negative feedback regulation of ACTH secretion in a rather specific way. Finally, on the basis of these results, a plausible model for the rapid rate-sensitive feedback regulation of ACTH secretion under stress was considered.