THE PITUITARY GROWTH HORMONE 375 



in vivo or in vitro does not accelerate the oxidation of palmitate or 

 acetate by rat-liver slices (Allen, Medes, and Weinhous, 1956; Green- 

 baum and Glascock, 1957; Baiiman et al., 1959). Our findings, as well, 

 as those of others who have employed direct criteria of fatty-acid oxi- 

 dation, are consonant with the view that growth hormone does not en- 

 hance the oxidation of fat by peripheral tissues. If this is indeed the 

 case, it is necessary to find a new explanation for the R.Q-depressing 

 effect of growth hormone, the decrease in carcass fat occasioned 

 by growth-hormone treatment, the ketogenic action of the hor- 

 mone, and the fate of the fatty acids mobilized after growth-hormone 

 administration. 



While a depression of the R.Q. can be brought about by an in- 

 crease in the proportion of fat in the oxidative substrate, a depression 

 in lipogenesis can yield the same result. That growth hormone can 

 indeed depress the synthesis of fatty acids from a variety of precursors 

 has been repeatedly demonstrated (Welt and Wilhelmi, 1950; Perry 

 and Bowen, 1955, 1957; Greenbaum and Glascock, 1957). An inhibition 

 of lipogenesis could most easily account also for the decreased fat 

 content of growth-hormone-treated animals and the ketogenic action 

 of the hormone ( Siperstein, 1959 ) . The disposition of the fatty acids 

 mobilized in response to growth-hormone treatment, however, is more 

 difficult to contend with. Available evidence does not permit a quanti- 

 tative evaluation of this process, although it does suggest that it is of 

 limited duration. It is most tempting to assume that the fat mobilized 

 after growth-hormone treatment is oxidized, but as we have seen, the 

 experimental evidence does not support this view^ One possibility is 

 that the mobilized fatty acids may serve as a source of carbon for the 

 synthesis of amino acids, thus contributing to the protein-anabolic 

 effect of growth hormone in the presence of an adequate nitrogen 

 supply. 



That such a process can occur was suggested by the following ex- 

 periments ( Hotchkiss and Knobil, 1960 ) . Hemidiaphragms from 

 young, normal rats were incubated for four hours in the presence of 

 labeled, albumin-bound palmitate. At the end of the incubation period 

 the protein of the diaphragms was purified (Kostyo and Knobil, 

 1959b) and was exhaustively extracted with a 2:2:1 mixture of ethyl 

 ether, ethyl alcohol, and chloroform. The extractions were continued 

 until no radioactivity was detected in the supematants. The proteins 

 were then plated and counted. As shown in Table VII, significant 

 quantities of palmitate carbon were recovered in the protein, the 

 higher values being observed when the specific activity of the palmitate 

 was high. More importantly, however, the incorporation of palmitate 

 carbon into protein carbon was significantly increased, as revealed by 

 paired analysis, when the concentration of palmitate was increased but 



