No abstract

Exogenously administered vasopressin (VP) augments ACTH secretion stimulated by CRH. This study was performed to elucidate the role of endogenous VP in potentiating CRH-induced ACTH secretion in man. Synthetic human CRH (100 micrograms) was injected iv into seven normal men after they had been water loaded (20 mL/kg; 60 and 30 min before CRH injection; WL-CRH test) and water deprived (water restriction for 18 h before CRH injection; WD-CRH test). Blood samples were obtained before and 5, 15, 30, 60, 90, and 120 min after CRH injection at 0900 h for determination of plasma ACTH, cortisol, arginine vasopressin (AVP), CRH, and catecholamine levels and osmolality. Urine was obtained immediately before and 120 min after CRH injection for determination of osmolality. The mean plasma AVP levels were significantly higher during the WD-CRH test [1.8 +/- 0.4 (+/- SE) to 1.9 +/- 0.4 pmol/L] than during the WL-CRH test (0.6 +/- 0.1 to 0.9 +/- 0.1 pmol/L). The mean plasma ACTH and cortisol levels rose significantly from basal (4.5 +/- 0.6 pmol/L and 320 +/- 20 nmol/L, respectively) to peak values of 14.0 +/- 2.1 pmol/L at 30 min and 700 +/- 50 nmol/L at 60 min, respectively, during the WD-CRH test. During the WL-CRH test, mean basal plasma ACTH and cortisol levels were 3.5 +/- 0.7 pmol/L and 420 +/- 50 nmol/L, respectively, and reached peak values of 7.7 +/- 1.1 pmol/L at 60 min and 550 +/- 40 nmol/L at 30 min, respectively. Both the mean peak levels and integrated ACTH and cortisol responses were significantly higher during the WD-CRH than during the WL-CRH test. There was no significant difference between the plasma CRH and catecholamine concentrations in both tests. These results suggest that endogenous AVP potentiates CRH-stimulated ACTH secretion and, thus, plays a physiologically significant role in regulating CRH-stimulated ACTH and cortisol secretion in man.

No abstract

No abstract

Abstract. The pharmacokinetics, responses of plasma ACTH and cortisol, urinary excretion of steroid hormones, and safety of MCI-028, a synthetic human corticotropin-releasing hormone (hCRH), were examined in eight healthy adult male volunteers after intravenous administration of 33, 100 and 200 µg of the drug. The disappearance of MCI-028 from plasma could be fitted to a biexponential decay curve, the plasma half-lives (T1/2) were 0.12 to 0.15 h for a phase, and 0.57 to 0.67 h for /3 phase. Plasma ACTH and cortisol concentrations and the urinary excretion of steroid hormones (particularly free cortisol) increased significantly in relation to the MCI-028 dose administrated. Although hot flushing and an increase in the heart rate were observed at higher doses, they were mild and transient. It is also considered that the urinary excretion of free cortisol after the administration of MCI-028 can be an index reflecting the functioning of this system.