Microsequencing evidence for the maturation of human proopiomelanocortin into an 18 amino acid β-melanocyte stimulating hormone [hβMSH(5–22)] in nonpituitary tissue

Sixty pmoles of a material with molecular size, immunological, and RP-HPLC characteristics identical to that of hβMSH(5–22) were purified from a bronchial carcinoid tumor responsible for the ectopic ACTH syndrome. The first 16 cycles of microsequencing revealed the following sequence: Asp-Glu-Gly-Pro-Tyr-Arg-Met-Glu-X-Phe-Arg-Trp-Gly-X-Pro-Pro-, identical to the first 16 amino acids of hβMSH(5–22). Since this material was recognized by an antibody which requires the free COOH-terminal Asp 22 residue, it can be assumed that it is indeed hβMSH(5–22). We also show that neither the 5 N acetic acid nor the 1 N HCl extraction procedure artefactually generated hβMSH-like material in normal or tumoral human pituitaries and in nonpituitary tumors. We conclude that hβMSH(5–22) is a normal maturation product of proopiomelanocortin in the human nonpituitary tissues which express its gene, including the hypothalamus and ACTH-secreting tumors.