PERIODICITY IN HUMAN BEINGS AND MICE 819 



Halberg, Visscher, and Bittner, 1953; Halberg et al, 1956; Vermund 

 et al, 1956). This also applies for human beings, as far as the eosino- 

 phil rhythm is concerned (Halberg et al, 1951; Hobbs et al, 1954; 

 Kaine et al, 1955). Moreover, it seems likely that the three variables 

 shown in Fig. 12 are not the only 24-hr periodic variables controlled 

 by the adrenals, since the effect of adrenal hormones has justly been 

 referred to as being almost "ubiquitous" (Sayers, 1950). On the other 

 hand, we know of at least one rhythm (studied with sufficiently fre- 

 quent sampling in verified cortical adrenal insufficiency) which is not 

 abolished by adrenalectomy, i.e., that in the iron content of human 

 serum (Hamilton et al, 1950; Howard, 1952). At any rate, it may be 

 emphasized that those variables illustrated in Fig. 12 have four charac- 

 teristics in common. First, they exhibit 24-hr periodicity, and second, 

 they respond in a typical fashion to corticoid administration, as do 

 many other body functions, including the corticoids of blood and urine 

 and the urinary 17-ketosteroids (Appel and Hansen, 1952; Doe et al., 

 1954, 1956; Forsham et al., 1944; Laidlaw et al., 1954; Migeon et al., 

 1956; Pincus, 1943; Pincus et al., 1948; Tyler et al., 1954). Thirdly, 

 and decisively for the experimenter interested in relations of the 

 adrenal to periodicity, these indices can be quantitatively studied in a 

 verified state of cortical adrenal insufficiency. Fourthly, the same in- 

 dices undergo critical changes in their 24-hr periodic behavior under 

 conditions of documented cortical adrenal insufficiency. It has there- 

 fore been suggested that the adrenals may be essential for the mainte- 

 nance of 24-hr periodicity in these body functions (Halberg and 

 Visscher, 1952; Halberg et al., 1951, 1956; Vermund et al., 1956). 

 Additional lines of evidence, while not meeting all the four criteria 

 listed above, nonetheless support as well as extend the conclusion that 

 the adrenals play an important role in the maintenance of 24-hr 

 periodicity. Thus, numerous reports on physiologic 24-hr periodicity 

 describe variables affected by (or dependent upon) adrenal regulation, 

 cortical as well as medullary (references in Halberg, Visscher, and 

 Bittner, 1953). Furthermore, adrenal periodicity, while it is responsive 

 to changes in the external and internal milieus, persists in the absence 

 of those periodic environmental changes which usually determine its 

 temporal placement within the 24-hr period. 



It has been suggested, therefore, that a 24-hr adrenal cycle (Hal- 



