AJP - Regulatory, Integrative and Comparative Physiology, Vol 234, Issue 1 39-R45, Copyright © 1978 by American Physiological Society
Fast, rate-sensitive corticosteroid negative feedback during stress
M. Kaneko and T. Hiroshige
Characteristics of the fast, rate-sensitive, negative-feedback regulation
of adrenocorticotropin secretion during stress was quantitatively analyzed
using rats anesthetized with pentobarbital sodium. Various levels of plasma
corticosterone were achieved during morning hours by infusing
corticosterone solutions of different concentrations. Blood was sampled
serially from the carotid artery. An increase in plasma corticosterone
concentration 15 min after intravenous, pulsed injection of histamine (230
microgram) during saline intravenous infusion was defined as the "control
response". When plasma corticosterone was rising during corticosterone
infusion, the response to histamine stimulus was distinctly inhibited
(fast, rate-sensitive feedback inhibition), whereas such an inhibition was
not observed when plasma corticosterone levels were not rising, regardless
of the absolute level. The critical rate of rise of plasma corticosterone,
at or above which the fast rate-sensitive feedback was manifested, was 4-6
microgram/100 ml per min. When three graded doses of histamine were
injected while plasma corticosterone levels were increasing at a rate of 6
microgram/100 ml per min, the absolute value of the inhibition observed was
independent of the administered dose of the stressor. A hypothetical model
for the mechanism of this feedback inhibition, based on the assumption that
the hormone effect was proportional to the rate of formation of
hormone-receptor complex, satisfied the quantitative characteristics of the
inhibition experimentally observed in this study.
