Plasma immunoreactive joining peptide in man: a new marker of proopiomelanocortin processing and corticotroph function.
Joining Peptide (JP) is a 30 amino acid fragment separating the N-terminal peptide and ACTH within their common polypeptide precursor POMC. Using antibody Jamie directed against the C-terminal amidated residue Glu-NH2 we studied the molecular weight forms and the variations of plasma immunoreactive (IR)-JP in man under various physiological, pharmacological, and pathological conditions. In 21 plasma samples from patients with ACTH hypersecretory syndromes from pituitary and nonpituitary tumors, IR-JP had the same elution pattern on Sephadex G-75 showing a predominant, if not single, peak corresponding to a mol wt of 7000 as expected for a JP-homodimer. Normal male volunteers at 0800 h had plasma IR-JP values ranging from undetectable (< 6 pmol/L) to 28 pmol/L; all values were suppressed by the overnight 1 mg dexamethasone test. Plasma IR-JP had circadian variations and responded to the metyrapone test in a manner strictly similar to that of ACTH and lipotropins (LPHs). One hundred and fifteen plasma samples covering a large range of pathological ACTH values (from 10(0) to 10(4) pmol/L) were also assayed by the JP and LPH RIAs. All three immunoreactivities strongly correlated with each other with a molar ratio close to 1:1. Discrepancies were observed in two situations where both IR-JP and IR-LPH were much higher than ACTH: they occurred in some patients with the ectopic ACTH syndrome and in all patients with chronic renal failure; they are explained by the further degradation of ACTH into corticotropin-like intermediary lobe peptide in the first case, by the prolonged plasma half-life of JP and LPH, compared to that of ACTH, in the second case. These data show that JP is a normal end-product of POMC processing in man which circulates in blood mainly as a homodimer. It provides yet another marker of the overall corticotroph function and may be used to unravel abnormal POMC processing in some nonpituitary tumors.
Phlipponneau
M
M
Centre de Recherche sur les Maladies Endocriniennes et Métaboliques, Hôpital Cochin, Paris, France.
Lenne
F
F
Proeschel
M F
MF
Girard
F
F
Luton
J P
JP
Bertagna
X
X
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000328:Adult; D002850:Chromatography, Gel; D002940:Circadian Rhythm; D003907:Dexamethasone; D005260:Female; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood; D008297:Male; D008797:Metyrapone; D008970:Molecular Weight; D009369:Neoplasms / Q000097:blood / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood*; D010903:Pituitary Gland, Anterior / Q000502:physiology*; D010911:Pituitary Neoplasms / Q000097:blood / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D008083:beta-Lipotropin / Q000097:blood
D010446:Peptide Fragments; D011333:Pro-Opiomelanocortin; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D008083:beta-Lipotropin; D008797:Metyrapone