Alpha-amidated peptides derived from pro-opiomelanocortin in human pituitary tumours.
Human pituitary tumours, obtained at surgery for Cushing's disease and Nelson's syndrome, were extracted and the content and molecular forms of pro-opiomelanocortin (POMC)-derived peptides determined by radioimmunoassay, gel chromatography, reversed-phase high-performance liquid chromatography (HPLC) and sequence analysis. In the tumours from patients with Cushing's disease the mean concentrations of amidated peptides relative to the total amount of POMC were as follows: alpha-MSH, 1.7%; amidated gamma-MSH (gamma 1-MSH), 8.5% and the peptide linking gamma-MSH and ACTH in the precursor (hinge peptide or joining peptide) in its amidated form (HP-N), 17.1%. The same relative concentrations in the tumours from patients with Nelson's syndrome were 8.5% (alpha-MSH), 7.5% (gamma 1-MSH) and 12.2% (HP-N). More than 95% of the ACTH(1-39) immunoreactivity eluted as synthetic ACTH(1-39) by gel chromatography and HPLC. The remaining ACTH(1-39) immunoreactivity eluted as partly glycosylated high molecular weight forms. All the alpha-MSH and its glycine-extended precursor ACTH(1-14) were of low molecular weight, mainly non- or mono-acetylated forms, but significant amounts of diacetylated analogues were also present. gamma 1-MSH and gamma 2-MSH immunoreactivities eluted as high molecular weight forms and were partly glycosylated. No low molecular weight forms of gamma 1-MSH or gamma 2-MSH could be detected in the pituitary tumours. Amidated hinge peptide was mainly of the 30 amino acid form. In conclusion, all the molecular forms of the amidated peptides detected in tumours from patients with Cushing's disease and Nelson's syndrome were similar to the molecular forms found in the normal human pituitary. The main difference between the tumours and the normal pituitary was the greater amount of peptides produced, particularly alpha-MSH and gamma 1-MSH.
Fenger
M
M
Department of Clinical Chemistry KK, University Hospital of Copenhagen, Denmark.
Johnsen
A H
AH
D000324:Adrenocorticotropic Hormone / Q000032:analysis; D002850:Chromatography, Gel; D002851:Chromatography, High Pressure Liquid; D003480:Cushing Syndrome / Q000378:metabolism; D006801:Humans; D009347:Nelson Syndrome / Q000378:metabolism; D010446:Peptide Fragments / Q000032:analysis*; D010911:Pituitary Neoplasms / Q000032:analysis*; D011333:Pro-Opiomelanocortin / Q000032:analysis*; D000521:alpha-MSH / Q000032:analysis
D010446:Peptide Fragments; D000521:alpha-MSH; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone