INTERACTION BETWEEN PLASMA CORTICOSTERONE CONCENTRATION AND ADRENOCORTICOTROPINRELEASING STIMULI IN THE RAT: EVIDENCE FOR THE RESET OF AN ENDOCRINE FEEDBACK CONTROL12

Abstract
Experiments were performed to test the hypothesis that the rapid rises in plasma corticosteroid concentration which follow many varied stimuli are caused by a reset of the negative feedback control of plasma corticosteroid concentration to regulate at higher levels. An intravenous dose of histamine, which when given alone produced after 15 minutes an increment in plasma corticosterone concentration of 20 μg/100 ml., was injected 15–30 seconds after an intravenous dose of corticosterone (12 μg/100 gm. B.W.) selected to produce the same increment. The resulting increment in plasma corticosterone concentration equalled that produced by the corticosterone alone: the exogenous corticosterone completely prevented the increased secretion of corticosterone ordinarily provoked by histamine. In a similar fashion, doses of corticosterone (5, 12, and 35 μg/100 gm. B.W.) were selected to produce increments in plasma corticosterone concentration less (10 and 18 μg/100 ml.) and greater (39 μg/100 ml.) than that observed after laparotomy (25 μg/100 ml.). When either of the smaller doses was injected 15–30 seconds prior to laparotomy, the resulting increment equalled, but did not exceed, that observed after laparotomy alone. When the highest close of corticosterone was injected just prior to laparotomy, the resulting increment in plasma corticosterone concentration equalled that seen after corticosterone alone. These results are those predicted by the reset hypothesis, which provides a basis for quantifying corticosteroid inhibition of adrenocorticotropin release, and they contradict the opposing view, that the release of adrenocorticotropin following noxious stimuli occurs independently of negative feedback control of plasma corticosteroid concentration.