[Analysis of dynamics of corticotropin-releasing factor (CRF) activity in the rat hypothalamus under stress]

Obviously, the analysis of dynamic changes in the hypothalamic activity of corticotropin-releasing factor (CRF) is essential for understanding of the central regulatory mechanism of ACTH secretion. However, the significance of the changes in CRF activity will be extremely lessened if the effect of CRF per se be modified at the pituitary level. In fact, Yates et al. (1971) reported that the CRF effect was potentiated by the presence of vasopressin. Therefore, in this study we attempted first to determine if vasopressin does potentiate the CRF action. Next, we analyzed some aspects of CRF dynamics in the rat hypothalamus under prolonged stress. (1) Potentiation of CRF action by vasopressin. This possibility was examined by the following approaches: i) Adrenocortical responses to various mild stressors (exposure to sound, i.p. injection of saline solution, tail cut) were greater in dehydrated rats than in normal controls. ii) Similarly, the adrenocortical response to intravenous injection of stalk-median eminence extract (SME) through the tail vein under Nembutal anesthesia was larger in the dehydrated rat than in control. iii) Prior to SME administration, vasopressin in a subthreshold dose was injected intravenously to assay rats pretreated with chlorpromazine (CPZ)-morphine (M)-Nembutal (Nb). The adrenocortical response to SME, injected into the carotid artery 1 min later, was found significantly to increase due to prior administration of vasopressin. iv) However, no potentiating effect of vasopressin was observed when SME and vasopressin (4 mU) were placed stimultaneously into the anterior pituitary tissue by the intrapituitary injection technique. v) In addition, no potentiating effect was observed in vitro incubation experiments under varying incubation conditions. Thus, it was shown that vasopressin has some potentiating effect on the stress response in vivo, but the effect is not at the pituitary level. (II) Analysis of dynamic changes in hypothalamic CRF activity. CRF activity was estimated by the intrapituitary injection method of Hiroshige, the plasma ACTH and corticosterone levels being followed simultaneously. Plasma ACTH was determined by radioimmunoassay partly with RCC-RIA Kit, and partly with ACTH antisera (kindly supplied by Dr. W.F. Ganong) by the method of Berson and Yalow. i) In intact normal rats, the response pattern of hypothalamic CRF activity under etherlaparotomy stress was characteristically biphasic, i.e., composed of rapid and slow phases, while the plasma ACTH and corticosterone showed a sustained high level over a 2 hr of observation period.