830 PERIODIC FUNCTIONS IN MAMMALS 



tions of corticoid are thus amenable to a simple interpretation. The 

 "ubiquitous" role played by corticoid (Sayers, 1950) may then be 

 attributed to an effect upon one or a few specific links of a normally 

 periodic chain (s) of metabolic events, and it need not be derived 

 from a more direct cortical adrenal participation in a large number of 

 biochemical processes. This same adrenal "driving" of cellular metab- 

 olism, at a rate and in a mode blended with superimposed and juxta- 

 posed controls (pituitary, hypothalamic, and other), could substan- 

 tially account for the efficiency of overall body adaptation to demands 

 from the outside. 



Other Integrative Functions 



It is on the basis of data from experiments involving gland removal, 

 with and without hormone replacement, that we have come to regard 

 the adrenal cortex as a pacemaker of 24-hr periodic mammalian 

 metabolism. Comparable data are not available, however, on the 

 problem of the extent to which the adrenal medulla participates in the 

 same phenomenon. It is well known that epinephrine in the adrenal 

 (Euler and Holmquist, 1934) as well as inter alia in the blood 

 (Lehmann and Michaelis, 1943) exhibits 24-hr periodicity, and what 

 is more important, it is one neurohumor, among other agents, that 

 affects many functions which also are regulated by corticoids (Hal- 

 berg, 1954a; Ramey and Goldstein, 1957). But the observation of 

 24-hr periodicity (a phenomenon which is common) cannot be used, 

 in itself, to suggest that the variable for which it is observed is responsi- 

 ble for 24-hr rhythms in other functions. Moreover, "neurohumoral" 

 regulations serve primarily the more immediate adaptations of the 

 body in "emergency reactions" (Cannon, 1929). It is probably via the 

 integration of their shorter-term effects that they exert an important 

 control upon 24-hr rhythms. The same considerations may apply for 

 rhythms noted in Minnesota for 5-hydroxytryptamine in mouse brain 

 (Albrecht et ai, 1956) and for the best known breakdown product 

 of 5-hydroxytryptamine, namely 5-hydroxyindoleacetic acid, in hu- 

 man urine (Figs. 16, 17) (Wadsworth, ^/fl/., 1957) (cf. Page, 1958). 



In Minnesota, we also have explored the role played by the pituitary 

 with respect to rhythms in epithelial mitoses (Zander et al., 1954) and 



