Corticotropin species, differences

Corticotropin (adrenocorticotropic hormone, ACTH) regulates the function of the adrenal cortex and has numerous other effects on metabolism. It contains 39 amino acids in the form of a random coil, owing to the presence of several proline residues that prevent helix formation. Species differences are seen in amino acids 25-39 the rest of the ACTH molecule is identical in all animals and humans. The first 24 amino acids are responsible for all of the biological action of ACTH synthetic human ACTHj 24 is known as cosyntropin. 

Highly purified polypeptides with corticotropic activity have been isolated from the pituitaries of different species including man. All these corticotropines contain a straight chain of 39 amino acides and species differences in chemical structure ocgur between positions 25 to 33 of the polypeptide chain. The exact structures of corticotropines from different species have been described by different authors (1,2 3, 4). 

The third approach has been followed predominantly in many laboratories. A comparison of differences in the primary structures of insulins, corticotropins, and cytochromes c from different species (see Table I) may serve as typical examples of these efforts. The data from these studies provide evidence of the extensive structural relationship between functionally identical proteins from different species this relationship decreases with the increased difference in species. 

The most valuable confirmation of this view to date is, without doubt, to be found in the known structures of homologous proteins and peptide hormones, that is compounds of identical biological function isolated from different species. As is well known, the primary structures of the homologous insulins, corticotropins, hypertensins, posterior pituitary hormones, and heme peptide sequences from cytochromes c are closely similar and differ only at certain definite sites in the peptide chains. These can, in particular, serve as a useful point of departure in a search for more general principles governing protein structure, and in the comparison of different proteins. 

Fig. 1. Processing of proopiomelanocortin (POMC) the precursor for the melanocortins and opiates in the mammalian pituitary gland. Processing occurs by proteolytic cleavage at sites of paired amino acids, some of which are shown here as dark bands. In both the anterior and the intermediate lobes, POMC is processed into an ACTH biosynthetic intermediate and into )J-lipotropin ()3-LPH 1-91). In the anterior lobe, subsequent processing yields the two biologically important products, ACTH 1-39 and )S-MSH. In the intermediate lobe, ACTH 1-39 is further processed to yield a-MSH (ACTH 1-13) and corticotropin-like intermediate peptide (CLIP). -MSH is derived, via y-MSH, from the 16-K fragment of POMC. This hormone varies in length in different species. Also in the intermediate lobe, /3-LPH is processed to produce p-endorphin 1-31. Many other small peptide fragments, of uncertain biological properties, are also produced, (from Strand et al., 1989).

The melanocyte-stimulating hormones are relatively small polypeptide chains found in the neurohypophysis. The two groups (a and P) of melanocyte-stimulating hormones differ essentially by the length of the polypeptide chain. MSH has been prepared from pig, beef, horse, monkey, and human pituitary. Fractionation of the extract produces the three active polypeptides a-MSH, j8-MSH, and corticotropin. Both a- and j5-MSH are found in all animals. There is no species variation in the amino acid sequence of the a-MSH. In contrast, a small species variation exists in the structure of jS-MSH as indicated in Table 8-6. All known MSH s including corticotropin have a common denominator a heptapeptide composed of methionine. 

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