A multiple timepoint study of N-terminal pro-opiomelanocortin in depression using a two-site recognition immunoradiometric assay

Abstract

N-pro-opiomelanocortin (N-POMC) is secreted from the same precursor as ACTH and beta-endorphin. Elevated plasma ACTH and beta-endorphin/beta-lipotrophin concentrations have been reported in depression, however there have been no previous studies of N-POMC. Twenty-five patients with major depression and 18 control subjects were studied at five timepoints to examine diurnal rhythm and the effect of a dexamethasone suppression test. N-POMC was measured using a newly developed two-site recognition immunoradiometric assay (IRMA). This demonstrated advantages of sensitivity, specificity and simplicity compared with existing radioimmunoassays. N-POMC exhibited a pattern of diurnal rhythm and suppression in response to dexamethasone as described for other POMC derived peptides. Depressed subjects had higher levels of N-POMC at 0900 h post-dexamethasone than did control subjects. In conclusion, the results of this study are consistent with a hypothesis of cosecretion of POMC-derived peptides. N-POMC has a similar pattern of abnormal concentrations to ACTH and beta-endorphin/beta-lipotrophin in depression. This constitutes probable evidence of POMC-derived peptide resistance to glucocorticoid feedback in this condition.