Characterization of pro-opiomelanocortin-derived peptides in pituitary and ectopic adrenocorticotrophin-secreting tumours.

The molecular forms of pro-opiomelanocortin in plasma of normal subjects and plasma and tissue extracts from patients with disorders of the hypothalamic-pituitary-adrenal axis have been characterized using gel filtration chromatography under acid dissociating conditions, and the molecular forms further investigated by high pressure liquid chromatography and affinity chromatography. A large molecular weight MSH/ACTH fragment was observed in all plasma samples chromatographed, although the proportions of this fragment were significantly greater in patients with the ectopic ACTH syndrome. A similar profile was observed in tumour extracts: a greater proportion of large molecular weight precursors was observed. Immunoreactive-gamma-MSH in extracts of ectopic tumours displayed marked and variable heterogeneity, and affinity chromatography with Concanavalin A-Sepharose indicated that this was due to differential glycosylation. High pressure liquid chromatography of a peak of amino terminal pro-opiomelanocortin (N-POC(1-76)) and 22 000 mol. wt MSH/ACTH indicated two peaks in each peptide, again possibly due to differential glycosylation. A possible neurointermediate lobe origin of atypical invasive pituitary tumours is discussed.