2. Endocrines and Populations 215 



the site of its origin in the hypothalamus and its exact identity remain mi- 

 known (Saffran et al., 1955; Porter and Jones, 1956; Porter and Rumsfeld, 

 1956; Clayton et al., 1957; Schally and Guillemin, 1959), and that the 

 release of ADH may be completely unrelated to the release of ACTH (Mc- 

 Donald et al, 1957; Schapiro et al, 1958) . It appears that this substance is a 

 small protein which is recoverable from hypophyseal portal blood, from the 

 neurohypophysis, or from extracts of appropriately selected portions of 

 the hypothalamus, and that it is probably loosely bound to and travels with 

 a much larger protein which is inactive with regard to the release of ACTH 

 (Porter and Rumsfeld, 1956; Guillemin et al, 1957; Schally and Guillemin, 

 1959). The activity of the corticothopin-releasing factor may be augented 

 by the simultaneous action of epinephrine (Saffran et al, 1955) . As is so 

 often the case, the solution to this problem may prove to be midway be- 

 tween, or to be a combination of, the two opposing views. It is possible 

 that there are hypothalamic substances, such as vasopressin, other than a 

 specific corticotropin-releasing factor which are capable of effecting the 

 release of specific ACTH fractions from the adenohypophysis. Recent- 

 evidence indicates that different stimulating factors are involved in ac- 

 tivating different adrenocortical functions (Fortier, 1956; Guillemin et al, 

 1958 ; Slusher, 1958 ; Nowell, 1959) . 



In spite of the existing uncertainty with regard to the nature of the speci- 

 fic factor or factors from the hypothalamus which stimulate the release of 

 ACTH, there is little doubt that hypothalamic substances carried to the 

 adenohypophysis by the portal system can stimulate the release of ACTH 

 in response to alarming stimuli, although Nowell (1959) has suggested 

 that emotional and systemic stress involve different pathways for the 

 release of ACTH. However, there are many other aspects of the overall 

 regulation of the secretion of adrenocorticotropin which are not clear at 

 the present time. One of these aspects is the control of the normal daily low- 

 level secretion of ACTH. There probably is a basal release rate of ACTH 

 which is independent of the hypothalamic-hypophyseal portal system and 

 which is sufficient for normal maintenance of adrenocortical function 

 (Fortier, 1957) . A number of workers maintain that the release of ACTH is 

 subject to hypothalamic control only in response to acute stressful stimuli 

 (Woodbury, 1958) . The level of circulating corticoids undoubtedly exerts a 

 control over the rate of secretion of ACTH, as circulating adrenocorticoids 

 are capable of inhibiting the release of ACTH under most circumstances, 

 although the more severe the stimulus, the greater the level of circulating 

 corticoids must be in order to block ACTH secretion (Sydnor and Sayers, 

 1954; Farrell and Laqueur, 1955; Sydnor et al, 1955; Richards and Pruitt, 

 1957). Fvu'thermore, Fortier (1959a, b) has shown that the corticotropin- 

 releasing effect of stress is influenced markedly by the level of circulating 



