THE PITUITARY GROWTH HORMONE 359 



it differs from the latter in exhibiting acute responses to a single injec- 

 tion of non-primate hormone, such as a fall in the concentration of 

 non-protein nitrogen and a rise in the level of non-esterified fatty acids 

 in the plasma (see below). On continued treatment, however, the 

 guinea pig fails to show any evidence of increased growth or nitrogen 

 retention (Hotchkiss and Knobil, 1960). Bovine growth hormone is 

 highly antigenic in the normal and hypophysectomized guinea pig, and 

 a small dose of bovine growth hormone administered to such animals 

 after sensitization by the same preparation results in anaphylactic 

 shock which is lethal in 90 to 100 per cent of the animals ( Hotchkiss 

 and Knobil, 1960). It would seem, therefore, that the failure of the 

 guinea pig to respond to daily treatment with bovine growth hormone 

 resides in the inactivation of the injected material by antibodies formed 

 against it, with consequent neutralization and loss of physiological ac- 

 tivity. Such a phenomenon would also explain the physiological effec- 

 tiveness of a single injection of bovine growth hormone to guinea pigs 

 not previously exposed to the hormone. It should be reiterated that an 

 acute response to bovine and porcine growth hormone cannot be ob- 

 served in a hypophysectomized rhesus monkey that has not previously 

 been exposed to these preparations (Goodman and Knobil, 1960), and 

 that a similar explanation is, in all probability, not applicable to the 

 situation in primates. 



On the mode of action of growth hormone 



Any consideration of the mode of action of growth hormone must 

 take into account the forbiddingly vast array of physiological and phar- 

 macological effects resulting from its administration. These have been 

 recorded in a massive literature which has been the subject of several 

 comprehensive reviews (Weil, 1955; de Bodo and Altzuler, 1957; 

 Ketterer, Handle, and Young, 1957; Russell and Wilhelmi, 1958). It is 

 not the intent of the present paper to duplicate these efforts. Limita- 

 tions of time and space will permit a discussion of only a few lines of 

 investigation bearing on the problem, with particular emphasis on our 

 own and related studies. 



The effect of growth hormone on some aspects of amUw-acid 

 metabolism. It has already been pointed out that growth of the fetus 

 and of the neonatal animal can proceed normally in the absence of 

 pituitary growth hormone; this suggests that the action of the hormone 

 is to sustain the functional integrity of processes which become de- 

 pendent on it at a critical time in the life of the young individual. 

 Presumably, in the absence of the hormone these processes gradually 

 slow and cease to function, with a resultant arrest of growth. Among 

 the processes most intimately associated with the production of new 



