This study was designed to establish definitively the nature of immunoreactive
lipotropin (IR-LPH) in human plasma and
tissue extracts. Using gel filtration, gel filtration under denaturing conditions, cationic exchange chromatography, immunoprecipitation, and radioimmunoassay, we have studied normal and tumorous human pituitaries, ectopic
ACTH- and LPH-secreting
tumors, plasma from normal subjects before and after
dexamethasone administration, and plasma from patients with
primary adrenal insufficiency and pituitary and nonpituitary
ACTH- and LPH-secreting
tumors. Except in the plasma and
tumors of occasional patients with
ectopic ACTH syndrome, the smallest IR-LPH appears to be lambda-
lipotropin (lambdaLPH), which is often the predominant and occasionally the only IR-LPH present. The other major
peptide appears to be betaLPH, a 91-amino
acid molecule that contains lambdaLPH as its 1-58 sequence. Larger immunoreactive materials were observed in some specimens, but the "big" LPH in one plasma was shown to be lambdaLPH bound to
IgG.The weak melanocyte-stimulating activity of LPH suggests that
ACTH may be the principal pigmentary
hormone in man. The fact that lambdaLPH, rather than betaLPH, is the predominant form in plasma suggests that the
enkephalin-
endorphin opiate peptides, which are contained in the "missing" 59-91 sequence from the betaLPH precursor of lambdaLPH, may be secreted in parallel with
ACTH under both physiological and pathological conditions in man.