PERIODICITY IN HUMAN BEINGS AND MICE 



827 



MALES 



FEMALES 



O 



Fig. 15. A single STH injection is reproducibly associated with increased 

 hepatic mitotic counts in mice if times of injection as well as of killing 

 are appropriate (Injection at 16:30; killing at about 12:30; light from 

 06:00 to 18:00, for instance). The same dose of STH did not elevate 

 mitotic count when given with the same interval between injection and 

 killing at certain other times. 



cortisone does so in doses of 5 Mg/20 g of body weight, while epine- 

 phrine in the same doses does not bring about the effect (Halberg et 

 al., 1956). Furthermore, desoxycorticosterone, in doses 100-fold 

 larger, barely reproduced the effect of 5 jug of cortisone. These findings 

 are in keeping with the assumptions that ( 1 ) the 24-hr periodicity in 

 the RSA of phospholipid phosphorus from mouse liver cytoplasm, 

 which is obliterated by adrenalectomy, is largely dependent upon the 

 periodic secretion of adrenal hormones, that (2) the cortex plays a 

 more critical role in this connection than the medulla, and that (3) 

 among the corticoids, 1 1-oxysteroids are more critical than 11-desoxy- 

 steroids. Furthermore, in the intact animal, the daily phospholipid 

 peak was found to occur at the time of periodic eosinopenia (Halberg 

 et al, 1956; Vermund et al, 1956) following with a lag of about 4 

 hr, the time of high blood levels of "corticosterone." For the time 

 being, the period A, during which periodic adrenal interaction with 

 cellular mechanisms occurs under physiologic conditions, may be 

 divided into two subperiods: Ai between the mitotic peak (of liver) 

 and the blood corticoid peak, and Ai; between the blood corticoid 

 peak and the hepatic phospholipid peak. 



Further work in endocrinology and metabolism may be facilitated 

 by information regarding the "right" time of hormone action (cf. 

 Kalmus' (1957) terminology) — and work on direct cellular effects of 



