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.
Centre de Recherche sur les Maladies Endocriniennes et Métaboliques, Hôpital Cochin, Paris, France.
M
M
Phlipponneau
F
F
Lenne
M F
MF
Proeschel
F
F
Girard
J P
JP
Luton
X
X
Bertagna
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