Increased Adrenocorticotropin, Cortisol, and Arginine Vasopressin Secretion in Primates after the Antiglucocorticoid Steroid RU 486:Dose Response Relationships*

Abstract

The antiglucocorticoid steroid, RU 486, elevated plasma ACTH concentrations when administered im at 0700 h in a dose of 1.0 mg/kg in nonhuman primates (Macacafascicularis; P < 0.05). The duration, but not the magnitude, of this response increased after 5.0 mg/kg RU 486 im; release of ACTH did not rise further after 10 mg/kg. Peak ACTH elevations occurred 1−2 h after RU 486 administration. Plasma cortisol concentrations peaked 4 h after RU 486 administration and the response was significant only after 5.0 mg/kg RU 486. Plasma arginine vasopressin (AVP) concentrations also increased after RU 486 but the increase occurred only after the 10.0 mg/kg dose {P < 0.05). The AVP elevation was greatest 4 h after 10 mg/kg RU 486 and was abolished by dexamethasone pretreatment. We conclude that: 1) RU 486 elevates plasma ACTH, cortisol,and AVP concentrations in a manner which is both dose and time dependent, 2) ACTH releaseoccurred at an order of magnitude lower dose than did AVP release, and 3) plasma AVP changes after RU 486 are glucocorticoid dependent.