604 DOWSE, NEUMAN, LANE, AND NEUMAN 



drate metabolism are indirect and, in large measure, dependent 

 upon experimental conditions. Thus, in intact dogs, citrate produc- 

 tion by bone is increased (Firschein et al., 1958); in calvarium and 

 metaphyseal chips no effects are seen in vitro sometimes (Borle et 

 al, 1960a; Neunian and Dowse, 1961; Cohn and Forscher, 1961), 

 though significant increases in labeled citrate (from labeled py- 

 ruvate, Lekan et al, 1960) or labeled CO- (from C-6-labeled glu- 

 cose via the TCA cycle, Cohn and Forscher, 1962Z?) are also reported. 



The most consistent finding is increased aerobic production of 

 lactate, and this, too, is not a dramatic change, usually 20 to 30 per 

 cent (Laskin and Engel, 1956; Borle et al, 1960a; Neuman and 

 Dowse, 1961 ) . Such a small shift in glycolysis has a number of plausi- 

 ble metabolic explanations, among which increased intracellular 

 levels of inorganic phosphate ( Pi ) is perhaps most appealing ( Egawa 

 and Neuman, 1963). Surely P, can be a controlling factor between 

 competing glycolytic and oxidative mechanisms. Increased P, could 

 increase aerobic lactate production and could also explain variable 

 condition-dependent changes noted above in the operation of the 

 TCA cycle. 



If we assume, for the moment, that parathyroid hormone does 

 increase P,, this change is in itself likely to be the result of some 

 more primary event such as a change in transport mechanisms of 

 ions in and out of the cell. 



This kind of speculation led us to examine the movement of labeled 

 inorganic phosphate in a variety of tissues, particularly bone, kidney, 

 and intestine. Hope for some modest success rested in the classic 

 phosphaturic activity ascribed to the hormone ( Albright and Reifen- 

 stein, 1948 ) . Indeed, it has been possible to show significant altera- 

 tions in the movement of labeled phosphate in all three tissues 

 (Egawa and Neuman, 1963; Borle et al, 1963). Of particular inter- 

 est, here, are studies on calvarium. Because calvarium contains a 

 fair quantity of bone mineral which represents a large pool of ex- 

 changeable phosphate, it was not possible to sample the cellular in- 

 organic phosphate directly. Instead, the acid-soluble ester fraction 

 was isolated as an indicator of intracellular label. As shown in Fig. 

 4, there was a significant increase in labeling of the ester-P fraction 

 in response to the hormone. 



