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 less than or equal to 6 micrograms/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 congruent to 5 micrograms/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 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)