322 CHOH HAO LI [18 



both C- and A^-terminal residues. Since the human and monkey hormones 

 have two and four cystine residues^'* respectively, it might be anticipated 

 that all — S — S — bridges would be located intramolecularly along the poly- 

 peptide chain. This was found to be the case when performic acid-oxidized 

 somatotropins were submitted to electrophoresis and ultracentrifugation. 

 Hence, it was proposed^" that human and monkey growth hormone have 

 the generalized gross structure shown in Fig. 10. 



Proposed Structure of the Human and Monkey Growth-Hormone Molecule 



Monkey: Phe ' ^ (Ala,Gly)Phe 



r 



Human: Phe ' ■ Ala(Tyr,Leu)Phe 



Fig. 10. Proposed gross structure for the human and monkey somatotropins. This model 

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



It has been demonstrated^" that the removal of C-terminal phenylalanine 

 from either human or monkey somatotropin by the action of carboxy- 

 peptidase does not result in any loss of the growth-promoting activity. It 

 is also possible to show that limited digestion of both somatotropins with 

 chymotrypsin does not lead to inactivation.^" Human somatotropin was not 

 inactivated by the action of chymotrypsin only if hydrolysis did not exceed 

 10%; longer digestion did diminish the biological activity. On the other 

 hand, the monkey hormone could be digested to 19% without any change 

 in the growth-promoting potency; as expected, digestion with the enzyme 

 to any further extent was found to result in the loss of the biological activity. 

 As in the case of bovine somatotropin,^'' these results seem to indicate that 

 the integrity of the intact protein is not essential for the activity of the 

 primate growth hormone. 



Whale Somatotropin. There has been only one report in the literature in 

 connection with growth-promoting activity of extracts of whale pituitaries. 

 In 1934, Valsö^^ reported that the content of growth-promoting activity in 

 the anterior pituitary of blue whale approached that found in bovine pitui- 

 taries. In recent investigations with H. Papkoff, growth hormone from 

 anterior lobes of whale pituitary glands* has been successfully isolated in 

 * The anterior pituitaries ranged in weight from 6-40 g., the average being about 21 g. 

 The whales were all of the humpback variety, which are commonly found off the Cali- 

 fornia coast and which attain an average length at maturity of around 40-50 feet. The 

 average interval post mortem before removal of the pituitary was about 20 hours. Once 

 removed, the gland was frozen as rapidly as possible and stored at — 15° C. until used. 



