ji é " i '^•' ' ^ -* ''^ ¥' >f ' i " -Sit 



18] STRUCTURE OF PITUITARY HORMONES 307 



residue replaces a glutamyl. This replacement of an uncharged residue 

 (serine) by a charged one (glutamic acid) has not to our knowledge been 

 encountered previously in connection with species variation among bio- 

 logically active peptides. Because of this structural difference, the isoelectric 

 point of the beef hormone (pH 7-0) is higher than that of pig ^-MSH (pH 

 5-8). The latter was found to migrate more slowly on starch in a pyridine- 

 acetate buffer of pH 4-93 than does the former (Fig. 3). Because of the 

 presence in the bovine MSH of serine at position 2 instead of glutamic 

 acid, it would be expected, on the basis of the known specificity of leucine 

 aminopeptidase (LAP),^^ that the rate of release of amino acids from this 

 hormone by the enzyme would be considerably slower than it would be 

 from the pig ^-MSH. That this was indeed found to be the case can be seen 

 from Fig. 4. 



According to the //; vitro frog skin assay,^^ beef MSH possesses a con- 

 siderably lower potency than does pig ^-MSH, It will be of interest to find 

 out whether this difference in activity between the hormones of the two 

 species is due mainly to the difference in the amino acid at position 2 of 

 the sequence, or whether other factors, such as secondary structure, are 

 involved. This question can be resolved only by the synthesis of the two 

 melanocyte-stimulating peptides.* Table 2 summarizes some physical and 

 chemical characteristics of the pig and beef hormones. 



II. ADRENOCORTICOTROPIC HORMONE 

 (ACTH, CORTICOTROPIN) 



It has been well established that hypophysectomy, in almost all the species 

 that have been studied, brings about a pronounced atrophy of the cortex 

 of the adrenal glands, whereas the medulla is affected scarcely at all.^-^^ 

 On the other hand, the implantation of anterior pituitary tissue or the injec- 

 tion of pituitary extracts into normal animals have as their chief effect a 

 marked hypertrophy of the adrenal cortex. Hence, the name adrenocortico- 

 tropic hormone (ACTH) has been employed to designate the active prin- 

 ciple in pituitary extracts that accomplishes repair of adrenal-cortical atrophy 

 in hypophysectomized animals,^ and in 1951 the term corticotropin was 

 adopted as the formal designation for preparations possessing ACTH 

 activity.^^ 



From unhydrolyzed ACTH concentrates, three groups of investigators have 

 succeeded independently in isolating the active peptide in pure form. In 

 1953, White,^^ in the Armour Laboratories, described the preparation of 



* For consonance with the pattern of terminology employed for the other pituitary 

 hormones, it was proposed that the melanocyte-stimulating hormones be called melano- 

 tropinsJ Following the precedent set by du Vigneaud'* for the vasopressins, the beef MSH 

 could be differentiated from the pig j3-MSH by designating the former seryl-melanotropin 

 and the latter glutamyl-melanotropin. These designations could be abbreviated as seryl- 

 JS-MSH and glutamyl- i3-MSH. 



