Feedback suppression of ACTH secretion by Cortisol in dogs: lags after large signals equal those following very small signals

Abstract

Previously, low stepwise infusions of Cortisol in resting adrenalectomized dogs (plateaux ≤ 6 μg/dL) were shown to reduce ACTH secretion only after 20 min. In the present study, large, steep-sloped cortisol signals were used to try to evoke faster feedback. Adrenalectomized male mongrel dogs were maintained on exogenous steroids until 48 h before the experiment. Of the 23 experiments on 15 dogs (under light pentobarbital anesthesia), 12 were on resting dogs, 7 on dogs stressed by variable insulin infusion (keeping plasma glucose at 18–40 mg/dL), and 4 stressed as above but with 4 h of low cortisol infusion (plasma [Formula: see text] 5 μg/dL) before applying the feedback signal. After a 50-min control period, a 30-min feedback period was initiated by one of two i.v. cortisol signals: (a) injection of 0.3 mg/kg or (b) infusion of 46 μg kg−1 min−1. Both raised plasma cortisol above physiological limits (within 2 and 6 min, respectively). In each experiment, 23 timed venous blood samples were assayed for plasma ACTH and cortisol. ACTH secretion rates were calculated continuously using a validated single-compartment method. Results from both types of cortisol signals were indistinguishable, and were thus pooled. In the unstressed dogs, control-period ACTH secretion of 0.97 ± 0.12 mU kg−1 min−1 showed no significant decline due to the feedback signal for 20.3 ± 1.4 min. In the stressed dogs the comparable values were 3.18 ± 0.92 mU kg−1 min−1 and 21.9 ± 3.2 min, and in the stressed Cortisol preconditioned dogs 0.78 ± 0.23 mU kg−1 min−1 and 21.0 ± 3.2 min. Thus at rest or in stress, these large cortisol signals evoked no more evidence of fast, rate-sensitive feedback than did very small signals.