A novel fragment of the corticotropin-β-lipotropin precursor

Abstract

The pituitary ACTH/MSH cells are virtual storehouses for biologically important peptides. In addition to corticotropins, melanotropins, opioid peptides and lipolytic peptides these cells contain large amounts of at least three different polypeptides (or small proteins) having tryptophan in the amino-terminal position (Trp-peptides)^1–5; their approximate molecular weight (MW) has been given as 14,000 (ref. 4). Nothing is known of their chemical properties and physiological significance. Experimental data indicate that the Trp-peptides in the ACTH cells are stored in the secretory granules³ to be released jointly with ACTH and other secretory products, such as β-endorphin and/or β-lipotropin (β-LPH)⁶. ACTH and β-LPH are formed from a large common precursor protein where they constitute the carboxy-terminal portion^7–14. Together the two peptides account for one-third to one-half of the molecular weight of the precursor and there has been considerable interest in the primary structure and possible physiological significance of the remaining amino-terminal portion¹⁵. The fact that the Trp-peptides occur in conspicuously high concentrations in the secretory granules of the ACTH/MSH cells prompted an investigation into their relation to the ACTH-β-LPH precursor protein. We have now isolated a glycopeptide with an apparent MW of ∼11,000 residing in the secretory granules of the ACTH/MSH cells from pig pituitary. The amino acid sequence of its amino-terminal part was found to be identical with the amino-terminal end of the bovine corticotropin-β-LPH precursor protein¹⁶. We propose that the isolated new fragment is identical with the amino-terminal portion of the precursor that remains after ACTH and β-lipotropin have been split off.