Progressive suppression of adrenocorticotropin secretion in resting adrenalectomized dogs by low stepwise infusions of cortisol.

Ten male mongrel dogs of 8.3-14.3 kg were bilaterally adrenalectomized and maintained on replacement steroids for 1 week. No exogenous steroids were detectable at the time of the experiment. Each dog, under light Nembutal anesthesia, received two stepwise primed constant infusions of cortisol (iv), each lasting 90 min (except in one dog with three infusions of 60 min). A recovery period of 80 min without cortisol infusion followed. Twenty-three venous blood samples were withdrawn for determination of plasma ACTH by adrenal cell suspension bioassay and 25 were withdrawn for plasma cortisol by fluorimetry at various times before, during, and after the cortisol infusions. ACTH secretion rates were calculated continuously from functions fitted to ACTH concentration and time data, using a validated single compartment approach with previously determined clearances and volumes. Initial high ACTH secretion rates of 1.0 +/- 0.2 mU/kg . min (range, 0.3-2.4) were reduced by 67.4 +/- 4.6% and 94.6 +/- 2.1% by the two cortisol infusions, which yielded cortisol plateau concentrations in plasma of 4.24 +/- 0.41 and 6.09 +/- 0.68 microgram/100 ml, respectively. This sensitive feedback response to low cortisol concentrations was delayed, with no effect for about 20 min and maximal effect reached within 1 h. There was no evidence of a fast rate-sensitive feedback. Some increases in ACTH secretion were seen during the recovery period (errors are +/- SEM).