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We previously demonstrated that acute injection of a pharmacological dose of oxytocin (2 IU) in humans decreased the concentrations of ACTH and cortisol, a neuroendocrine action opposite that of vasopressin. In the present work the effect of continuous infusion of lower doses of oxytocin was tested. Plasma oxytocin was also measured using an oxytocin RIA to study the dose-response relation. Infusion of oxytocin (8 mIU/min for 30 min) resulted in a plasma oxytocin level of 9.9 +/- 1.4 (+/- SD) muIU/ml and induced a decrease in the plasma concentration of ACTH in three of four normal subjects. Infusion of oxytocin at the rate of 16 mIU/ml for 30 min resulted in plasma oxytocin level of 17.7 +/- 1.6 muIU/ml and decreases in plasma ACTH and cortisol concentrations in all six subjects tested. Increasing the oxytocin dose from 32 to 64 and 128 mIU/min for three additional 30-min periods induced more pronounced decreases in plasma ACTH and cortisol. In each subject, there was a highly significant inverse relationship between plasma oxytocin, and ACTH and cortisol (r = -0.85 to -0.99). During saline infusion, a significant inverse relationship with a 10-min lag period between plasma oxytocin and ACTH (r = -0.55) was found in only one of six subjects. These data demonstrate that infusion of exogenous oxytocin leading to plasma levels approximately 10 times higher than normal induced consistent decreases in corticotropic function. Because the oxytocin concentration in portal blood is approximately 300 times higher than that in peripheral blood, it is likely that the inhibitory action of oxytocin on ACTH secretion is of physiological significance.
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