AN OXYTOCIN PRECURSOR INTERMEDIATE CIRCULATES IN THE PLASMA OF HUMANS AND RHESUS-MONKEYS ADMINISTERED ESTROGEN

Estrogen releases into plasma the human oxytocin neurophysin, previously termed the estrogen-stimulated neurophysin. Because oxytocin and its neurophysin are synthesized as part of a common precursor, stimuli which release the hormone should also release neurophysin and vice versa. However, release of oxytocin with its neurophysin has been difficult to demonstrate by immunological assay in humans administered estrogen. Under this condition, the oxytocin immunoreactivity that is released with the oxytocin neurophysin is a novel peptide which is antigenically similar to oxytocin yet is not oxytocin. Co-release of the oxytocin-like peptide with oxytocin neurophysin suggested that the oxytocin-like immunoreactivity may be a partially processed form of oxytocin. To test this hypothesis the synthetic oxytocin precursor intermediates oxytocin-glycine (G), oxytocin-glycine-lysine (GK), and oxytocin-glycine-lysine-arginine (GKR), were tested for cross-reactivity with the various oxytocin antisera used in this laboratory to distinguish the oxytocin-like peptide from oxytocin. Oxytocin-G, but not oxytocin-GK or GKR, showed extensive cross-reactivity with the oxytocin antisemiti (Ab1), which is known to detect the oxytocin-like peptide of human plasma. Plasma from men and rhesus monkeys administered estrogen and from pregnant women was separated by HPLC and oxytocin Ab1 immunoreactivity was eluted from the column with the same retention time as synthetic oxytocin-G. Estrogen releases an oxytocin precursor intermediate into the circulation of humans and monkeys and may exert an important effect upon posttranslational cleavage of the oxytocin prohormone. These observations suggest a heterogeneity in the intraneuronal posttranslational processing of the oxytocin precursor in estrogen-treated versus nonestrogen-treated primates. © 1990 S. Karger AG, Basel.