224 



G. Nichols, jr. 



This species' variability may be even better illustrated by the difference in the 

 uptake of glycine into male rat and mouse bone following estradiol treatment. As 

 shown in Fig. 7 (Vaes and Nichols, 1962) incorporation into bone was depressed 

 by estradiol in rats while stimulated in mice. These findings, which confirmed histo- 

 logic observations, indicate that in rats estrogens inhibit bone resorption while in 

 mice they stimulate new bone formation. Thus the accumulation of cancellous bone 

 in the marrow cavities of the long bones which results in both species occurs for 

 entirely different reasons. Clearly, these observations show the need to explore 

 hormone effects in depth if understanding is to be obtained sufficient to predict 

 actions in other tissues and in other species — predictions which are so important in 

 the clinic. The considerations outlined earlier indicate the kind of question which 

 must be asked: Is the observed change the result of changes in new bone synthesis or 

 old bone resorption or both? Is the hormone affecting membrane permeability, 

 membrane stability, enzyme activity, the biosynthesis of proteins through nuclear 

 mechanisms, or some combination of these factors? 



While the changes shown in the last 2 diagrams were relatively small, very marked 

 changes in specific aspects of bone metabolism occur when certain hormones are 

 absent. Fig. 8 shows the profound depression in the rate of bone collagen biosynthesis 

 which we have recently found in hypophysectomized and thyroidectomized rats. 

 Lesser changes of the same type were also found in O, uptake and proline incorpo- 

 ration into the cells while lactate production was not significantly changed. Inter- 

 estingly none of these effects were reproduced by parathyroidectomy alone. Again the 

 details remain to be explored, but the relation of these observations to the growth 

 failure noted in animals and patients deprived of pituitary or thyroid secretions 

 during the growth phase seems clear. 



M Normal 



I I Hypophysechmized 



[^ Thyro-Parafhyroidectomized 

 Q Paraf-hyroidecfomized 



Changes 



Lacfafe 

 producfion 



letabolic indices induced in rat b 

 organs 10 days before sacrifice 



One other indication of the importance of these hormones in the control of bone 

 cell metabolism has recently been pointed out by Johnston and Deiss (1965). The 

 presence of an intact pituitary seems to be necessary for the development of some of 



