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18] STRUCTURE OF PITUITARY HORMONES 319 



enzyme/hormone ratio of 1/300, did not result in inactivation if hydrolysis 

 were allowed to proceed up to about 25%; however, the biological potency 

 was abolished by longer digestion. Thus, it should be noted that if an active 

 digest is desired, the extent of hydrolysis must not be permitted to exceed 

 30%. The non-protein nitrogen can be separated from the whole digest either 

 by dialysis or by treatment with a 5% solution of trichloroacetic acid. It 

 was demonstrated by biological assay that the growth-promoting activity 



Proposed Structure of the Beef Growth-Hormone Molecule 



Phe, Ala. -— — ^— ^^■— ■^— ^^ Ala Phe, Phe. 



(S-S)^ 

 Alo, Phe. Ala. ^— ^^^^^^-i— 



J 



Fig. 9. Proposed gross structure for the bovine somatotropin molecule. This model is 

 somewhat speculative and structures other than that shown here are possible. 



resides in the remaining components (the core), which are non-dialyzable 

 and insoluble in the trichloroacetic acid solution.'^ 



Boundary electrophoresis of the core has not revealed any component 

 that behaves like the untreated bovine hormone. A^-Terminal analysis of the 

 core reveals a number of new residues (threonine, serine, tyrosine, lysine, 

 etc.), in addition to phenylalanine and alanine ; if we assume that the ter- 

 minal phenylalanine and alanine residues have come from the undigested 

 bovine hormone, it can be estimated that the native hormone in the core 

 amounts to less than 20%, a percentage certainly not suflEicient to account 

 for the biological activity of the core. From these results, it may be con- 

 cluded that the activity does not depend upon the integrity of the bovine 

 protein, and that the growth-promoting activity resides in a center (or 

 centers) of activity in the molecule. 



Human and Monkey Growth Hormones. In recent years, many attempts 

 have been made to apply growth hormone clinically to humans as an effec- 

 tive therapeutic agent, but these attempts have met with disappointment.'* 

 One of the obvious explanations for this failure is that the bovine growth 

 hormone is chemically different from the hormone derived from human 

 glands. Indeed, it has been shown that the growth hormone prepared from 

 fish pituitaries is active in fish,'^ but not in rats;'^ and that monkeys are 

 not responsive to bovine growth hormone, whereas they are responsive to 

 growth hormone prepared from pituitaries of their own species."'^ Our 

 recent investigations with human and monkey pituitary glands indicate that 

 the human and monkey growth hormones are similar to each other in struc- 

 ture and properties, but that they both differ completely from the hormone 

 molecule isolated from the pituitaries of cattle.''^ -^^ 



