Comparison of canine corticosteroid responses to mean and phasic increases in ACTH

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Abstract
To determine the dynamics and magnitudes of adrenal corticosteroid responses to ACTH, arterial plasma ACTH and corticosteroid concentrations were measured in conscious dogs during infusions of ACTH or saline. Synthetic .alpha.1-24-ACTH was infused at rates of 300, 900 or 4500 ng/30 min either as constant infusions or as 3 equal short infusions at 10-min intervals. In dogs infused with saline, plasma ACTH fluctuated, whereas corticosteroids did not, suggesting that ACTH is screted episodically in dogs as in man. The magnitudes of the plasma corticosteroid responses to ACTH infusions were linearly related to the logarithm of the total amount of ACTH infused in 30 min and not to the pattern of administration. In all ACTH infusion experiments, the lag between an increase in arterial ACTH and corticosteroids was not less than 3 min. Mean ACTH half-disappearance time, metabolic clearance rate, and volume of distribution estimated from the different experiments ranged between 1.8 and 2.1 min, 24 and 38 ml .cntdot. kg-1 .cntdot. min-1, and 95 and 114 ml/kg, respectively. Collectively, these results explain the apparent paradox that corticosteroid responses to ACTH-releasing stimuli can be initiated before a detectable increase in ACTH above the highest control value.