Potentiation of the hCRF-induced release of ACTH in man by an opioid antagonist.

Administration of synthetic human corticotropin-releasing factor (hCRF; 2 micrograms/kg body weight) to six normal male subjects produced a significant rise in plasma ACTH, followed by an increase in circulating cortisol. Simultaneous treatment with the opioid antagonist naloxone (1.6 mg i.v. bolus, followed by an infusion at a rate of 1.2 mg/h) significantly potentiated the hCRF-induced rise in ACTH and enhanced the cortisol response to hCRF. It is suggested that naloxone acts by antagonizing an inhibitory ultra-short-loop feedback effect of coreleased beta-endorphin on pituitary corticotrophs, thereby amplifying the net effect of hCRF, i.e., the release of ACTH.