Microsequencing evidence for the maturation of human proopiomelanocortin into an 18 amino acid beta-melanocyte stimulating hormone [h beta MSH(5-22)] in nonpituitary tissue.
Sixty pmoles of a material with molecular size, immunological, and RP-HPLC characteristics identical to that of h beta MSH(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 h beta MSH(5-22). Since this material was recognized by an antibody which requires the free COOH-terminal Asp22 residue, it can be assumed that it is indeed h beta MSH(5-22). We also show that neither the 5 N acetic acid nor the 1 N HCl extraction procedure artefactually generated h beta MSH-like material in normal or tumoral human pituitaries and in nonpituitary tumors. We conclude that h beta MSH(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.
Bertagna
X
X
Centre de Recherche sur les Maladies Endocriniennes, Hôpital Trousseau, Paris, France.
Seidah
N
N
Massias
J F
JF
Lenne
F
F
Luton
J P
JP
Girard
F
F
Chretien
M
M
D000595:Amino Acid Sequence; D002283:Carcinoma, Bronchogenic / Q000032:analysis*; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008175:Lung Neoplasms / Q000032:analysis*; D009074:Melanocyte-Stimulating Hormones; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D010911:Pituitary Neoplasms / Q000032:analysis*; D011333:Pro-Opiomelanocortin / Q000302:isolation & purification; D011863:Radioimmunoassay
D010446:Peptide Fragments; C060221:MSH, beta, (5-22); D011333:Pro-Opiomelanocortin; D009074:Melanocyte-Stimulating Hormones