Measurement of N-Terminal (1–76) of Human Proopiomelanocortin in Human Plasma: Correlation with Adrenocorticotropin*

Abstract

A sensitive and specific homologous RIA for human N-terminal (hNT) of proopiomelanocortin has been developed. The lower limit of sensitivity of the assay is 10 pg/tube. The assay is specific for hNT in that human ACTH, α-melanotropin, β-lipotropin, and β-endorphin exhibit no cross-reaction. Serial dilutions of unextracted human plasma obtained from normal subjects during insulin-induced hypoglycemia test, patients with Cushing's disease, Nelson's syndrome, Addison's disease, and chronic renal failure display a parallel displacement with hNT in the assay. Mean basal immunoreactive (IR) hNT (mean ± SE) in normal subjects, patients with Cushing's disease, Nelson's syndrome, Addison's disease, and chronic renal failure was less than or equal to 100 pg/ml, 280 ± 60 pg/ml, 19,666 ± 6,749 pg/ml, 11,295 ± 8,730 pg/ml, and 545 ± 73 pg/ml, respectively. Mean IR-ACTH (mean ± SE) in these patients was 22 ± 4 pg/ml, 38 ± 7 pg/ml, 1,751 ± 1,191 pg/ml, 1,112 ± 992 pg/ml, and 60 ± 13 pg/ml, respectively. Insulin-induced hypoglycemia in subjects with normal pituitary function caused a concomitant release of equimolar hNT and ACTH. A strong correlation was found between IR-hNT and IR-ACTH in plasma of normal subjects during insulin-induced hypoglycemia (r = 90, P < 0.001) as well as in plasma of patients with various disorders of pituitary-adrenal axis or with chronic renal failure (r = 0.93, P < 0.001). Gel permeation chromatography of human plasma revealed a major peak of IR-hNT in the elution volumes of authentic hNT (mol wt, 12K). These results indicate that hNT of 12K is the predominant circulating form in human plasma. Measurement in plasma may indicate the state of secretion and/or metabolism of peptides related to the expression of the proopiomelanocortin gene from human pituitary. Since its plasma levels are much higher than ACTH and since measurement of plasma IR-hNT is much simpler than ACTH which requires extraction before assay, it is conceivable that measurement of hNT may provide a more useful tool for diagnosis of patients with various disorders of ACTH secretion. J Clin Endocrinol Metab56: 791, 1983)