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Role of Endogenous Arginine Vasopressin in Potentiating Corticotropin-Releasing Hormone-Stimulated Corticotropin Secretion in Man^*

Third (T.W., M.Ku., S.I., M.Ko., KM., F.T., E.U., N.S.) and First (K.T., M.H., T.H., S.M.) Departments of Medicine, Teikyo University School of Medicine 2-11-1, Kaga, Itabashi-ku, Tokyo 173, Japan

Address all correspondence and requests for reprints to: Koshi Tanaka, M.D., First Department of Medicine, Teikyo University School of Medicine, 2-11-1, Kaga, Itabashi-ku, Tokyo 173, Japan.

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 ng) 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.

^* This work was supported in part by a Research Grant for Intractable Diseases from the Japanese Ministry of Health and Welfare, a research grant from the Japanese Ministry of Education, Science, and Culture, and a research grant from the Sankyo Foundation of Life Science.

Received May 21, 1987.

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