Proopiomelanocortin is the predominant adrenocorticotropin-related peptide in human cerebrospinal fluid.

High mol wt forms of immunoreactive ACTH and beta-endorphin (beta EP) are present in cerebrospinal fluid (CSF). We have quantified these peptides directly in the CSF of 26 patients undergoing routine myelography, using a panel of monoclonal antibody-based two-site immunoradiometric assays, specific for ACTH precursors (both POMC and pro-ACTH cross-react 100%), POMC, ACTH, and beta EP. The mean +/- SD levels of POMC in CSF were 530 +/- 150 pmol/L similar to total ACTH precursor immunoreactivity (414 +/- 83 pmol/L). By comparison, the CSF levels of ACTH (3.2 +/- 0.6 pmol/L) and beta EP (6.7 +/- 2.9 pmol/L) were 100-fold lower. POMC, by virtue of its 1% cross-reactivity in the ACTH immunoradiometric assay, could have also accounted for the ACTH immunoreactivity in CSF. Sephadex G-75 chromatography of CSF confirmed the presence of a single major peak of ACTH precursors eluting at the position of POMC (31K), while ACTH immunoreactivity was not detected at the position of ACTH-(1-39) (4.5K). We also studied the effect of exogenous glucocorticoids on CSF POMC peptides by giving 2.5 mg dexamethasone (0.5 mg, orally, every 6 h for 24 h) to a similar group of age-matched patients before lumbar puncture. No significant differences in CSF peptide content were observed between the two groups. These data suggest that the unprocessed precursor molecule POMC is the predominant peptide of the POMC family in human CSF and should always be considered when interpreting data involving ACTH or other component peptide immunoreactivity in this biological fluid.