LATE FEEDBACK EFFECTS OF HYPOTHALAMIC-PITUITARY-ADRENAL AXIS HORMONESIN HEALTHY-SUBJECTS

We tested the hypothesis that hypothalamic-pituitary-adrenal (HPA) axi s hormones exert prolonged negative feedback on corticotropin (ACTH) s ecretion. Ten healthy subjects underwent a standard protocol 4x and ea ch rime received IV, under double blind conditions and in random order , corticotropin-releasing hormone (CRH) 1 mu g/kg, co-syntropin (ACTH( 1-24)) 0.25 mg, cortisol (hydrocortisone) 15 mg, or placebo. Subjects had a venipuncture for cortisol and ACTH levels at 0900h on Day 1, the n had IV insertion and cortisol and ACTH levels measured at 1600 and 1 855h. The test substance was given at 1900h and cortisol and ACTH leve ls were monitored until 2300h, when the IV's were discontinued. Subjec ts then had venipunctures for cortisol and ACTH levels at 0900 and 160 0h on Day 2 and 3. Hormones had the expected acute effects. Hormones d id not differ from placebo in effects on cortisol levels measured over Days 2 and 3. There were significant differences between test substan ces in effects on afternoon ACTH levels on Days 2 and 3, with ACTH lev els increasing significantly less from baseline to Day 2 and 3 after C RH administration than after placebo, and tending to increase less fro m baseline to Day 3 after ACTH administration than after placebo. Exam ination of Day 2 and 3 morning ACTH levels showed a significant intera ction between the test substances and rime (Day 2 vs. 3), and interpre tation of this interaction is not straightforward. We conclude that CR H and possibly ACTH exert late inhibitory effects on ACTH secretion me asured in the afternoon of the 2 days following hormone administration . (C) 1998 Elsevier Science Ltd. All rights reserved.