852 PERIODIC FUNCTIONS IN MAMMALS 



of the lighting schedule are exerted primarily upon the phase of a 

 given rhythm in relation to the environment and not necessarily upon 

 the "maintenance" of rhythm (see qualifications above). 



But quite apart from the effect of illumination, it may also be seen 

 from Figs. 19-25 that the amplitude of the various rhythms is not the 

 same. With reference to carbohydrate metabolism, for example, it 

 may be noted that percentage-wise the daily change in blood glucose 

 is much smaller as compared to that in liver glycogen. In mice feeding 

 ad libitum, glycogen practically disappears from the liver once a day; 

 glucose while exhibiting a significant 24-hr periodic change, is present 

 in blood at all times in relatively large amounts. Such information on 

 the periodic behavior of various aspects of metabolism is of obvious 

 interest to students of bioassay. To cite an example, for studies of drug 

 effects upon blood glucose, periodicity analysis seems to offer several 

 advantages; (1) one may compare the effect of the agent tested at 

 high and low levels of liver glycogen, while the blood sugar levels are 

 relatively high and predictable; (2) one can do so without being 

 forced into dealing with starved animals; instead, one works with 

 animals in as physiologic a condition as feasible; and moreover, (3) 

 one can carry out the work whenever one wishes since by an ap- 

 propriate control of illumination the desired physiologic state can 

 be shifted to any convenient clock hour (cf. also Elfvin et ai, 1955; 

 Pitts, 1943). Figure 23 reveals that this last consideration is particu- 

 larly pertinent for the student of DNA metabolism since the peak in 

 the relative specific activity (RSA) of hepatic DNA in mice kept under 

 usual lighting conditions occurs at about 4 a.m. Likewise, it may be 

 desirable to shift to a more convenient hour the peaks of the RSA of 

 the hepatic RNA or phospholipid, which usually occur at 8 p.m. All 

 this can be done by a shift in lighting regimen. The advantages derived 

 from physiologic work in defined phases of daily cycle may be illus- 

 trated by a reference to the effect of pituitary growth hormone upon 

 hepatic mitoses in the immature intact mouse; after hormone ad- 

 ministration an increase in mitotic count will be seen consistently 

 in one phase of mitotic rhythm, but not in another (Litman et al., 

 1958) (Fig. 15). For the study of certain other problems as well 

 (Halberg, Halberg, and Bittner, 1955; Halberg and Stephens, 1958) 

 the selection of the "right time" has proved as important as our 



