Modulatory effects of corticotropin-releasing factor on the delayed corticosteroid feedback in humans: implications...

We recently demonstrated the presence of a delayed phase of glucocorticoid feedback on nonstress-induced ACTH secretion in normal volunteers. In this study, we investigate the effects of corticotropin-releasing factor (CRF) on that delayed feedback pathway with an attempt to determine the sites on which glucocorticoid exerts its delayed feedback effects. Thirty normal subjects were subjected to study and each subject received a single midnight dosage of 30 mg/kg BW metyrapone before each test. The whole experiment was divided into two studies. In study I, we found that ovine CRF (oCRF) 1 microgram/kg BW alone as an IV bolus injection caused an increase in the plasma ACTH level, which persisted for at least 120 minutes. Continuous infusion of cortisol 25 mg/h alone for two hours produced a significant decrease in the plasma ACTH level; this fall of ACTH began 30 minutes after the onset of cortisol administration. When IV bolus injection of oCRF 1 microgram/kg BW and the continuous infusion of cortisol 25 mg/h for two hours were both given, the plasma ACTH level increased firstly and then decreased 60 minutes after the onset of cortisol administration, progressing thereafter to the end of the study. Study II showed in those who received the IV bolus injection of human CRF (hCRF) 100 micrograms and the continuous infusion of cortisol 25 mg/h for two hours, the plasma ACTH level increased firstly and began to decline 45 minutes after the onset of cortisol administration, progressing thereafter to the end of the test.(ABSTRACT TRUNCATED AT 250 WORDS)