THE PITUITARY GROWTH HORMONE 357 



rather than the mere deposition of fat and the sequestration of salts and 

 water. 



Species specificity 



The many convincing demonstrations of the potent growth- 

 promoting properties of pituitary extracts in experimental animals 

 prompted a number of clinical investigators to assay these preparations 

 in cases of human dwarfism. These early trials with rather crude prep- 

 arations of ox pituitary glands were disappointing. When highly puri- 

 fied preparations of ox and pig pituitary growth hormone became avail- 

 able, attempts to demonstrate their physiological actions in man were 

 renewed. For the most part these attempts were unsuccessful, and 

 they led to the rather unsatisfactory conclusion that the available 

 growth-hormone preparations were ineffective in man. Exhaustive 

 studies with bovine and porcine growth hormone in normal and hy- 

 pophysectomized rhesus monkeys led to similar conclusions: namely, 

 that these preparations were inactive in this species, as judged by a 

 large number of morphologic and metabolic criteria (Knobil and 

 Creep, 1959). Similarly, these growtli-hormone preparations, which 

 were highly active in rats, dogs, and cats, were reported to be in- 

 effective in the guinea pig (Mitchell ef al., 1954; Knobil and Creep, 

 1959). These findings led to considerable speculation regarding the 

 underlying reasons for the apparent inefficacy of bovine and porcine 

 growth-hormone preparations in these species, but the matter was 

 clarified with the finding that growth-hormone preparations isolated 

 from monkey pituitary glands were highly effective in the rhesus 

 monkey (Knobil et al., 1957) and in man (see Raben, 1959). Similarly, 

 growth hormone prepared from human pituitary glands is active in man 

 (Raben, 1959) and the rhesus monkey (Knobil and Coodman, 1959). 

 These primate growth-hormone preparations are as active in the rat as 

 they are in man and the monkey; thus they differ fundamentally from 

 ox and pig preparations, which are inactive in primates but fully ef- 

 fective in the rat. The latter species, however, is refractory to fish 

 growth hormone, a preparation which shares with bovine growth hor- 

 mone the ability to stimulate the growth of fish ( Wilhelmi, 1955 ) . Fur- 

 ther studies have revealed that the physicochemical characteristics of 

 fish growth hormone differ from those of the bovine molecule (Wil- 

 helmi, 1955) and that primate growth-hormone preparations have 

 markedly different properties when compared with those from other 

 mammalian species ( Table I ) . These dissimilarities are such that com- 

 petitive inhibition between monkey and bovine growth hormones could 

 not be demonstrated in the rhesus monkey (Knobil et al., 1958), and, 

 as might be expected, the primate preparations proved to be immuno- 



