A novel human pituitary peptide containing the γ-MSH sequence

Abstract

It is well established that ACTH and β-lipotropin (LPH) originate from a common precursor molecule1–3. Recently the complete complementary DNA sequence of the bovine precursor was reported4, and within the cryptic sequence of this molecule is a third melanocyte stimulating hormone (MSH) region tentatively named γ-MSH4. The signal peptide of this molecule consists of 26 amino acids in both the rat5 and mouse6. Pulse-chase experiments using both rat and mouse pituitary cells, showed the gradual maturation of this common precursor to proceed via the initial cleavage of the carboxy terminal β-LPH, followed by release of ACTH, leaving an NH2-terminal extension of about 105 amino acids, which does not seem to undergo appreciably further maturation1–3,7. It is within the sequence of this NH2-terminal extension that γ-MSH is located4. It is not yet clear what the biological role of this molecule is and whether γ-MSH itself is released. Recently, it was shown that a synthetic 12 amino acid bovine γ-MSH fragment possessed very little melanophore-stimulating activity as compared to α-MSH8. We report here the successful purification of the human NH2 terminal cryptic peptide, its amino acid composition and present some of its tryptic fragments. The data show that human and bovine γ-MSH have identical amino acid composition.