Vasoactive intestinal polypeptide modulates the estradiol-induced prolactin surge by entraining oxytocin neuronal activity.

In female rats, estradiol is responsible for a circadian secretory prolactin (PRL) pattern which requires an intact suprachiasmatic nucleus (SCN). SCN outputs involved in this secretory profile remain elusive. Because oxytocin has been proposed to stimulate PRL secretion, we investigated whether the projections of vasoactive intestinal polypeptide (VIP) from the SCN to neurons producing oxytocin in the paraventricular and periventricular nuclei (PVN and PeVN, respectively) are responsible for timing PRL surges induced by estradiol (E(2)). E(2)-treated ovariectomized rats received an injection of antisense or random-sequence oligodeoxynucleotide for VIP in the SCN and blood samples were taken for PRL measurements by radioimmunoassay. Additionally, the percentage of oxytocin-positive neurons immunoreactive to FOS-related antigens was determined in the PVN and PeVN, as an index of neuronal activity. In the PVN, oxytocinergic neuronal activity increased in the early evening regardless of E(2) treatment, whereas E(2) induced an increase of activity in the PeVN. VIP antisense attenuated this increase observed in both neuronal populations. Additionally, in the PeVN, VIP antisense advanced this increase by 2 h (from 19:00 h to 17:00 h). This same effect was observed in the PRL surge that occurred at 17:00 h in the VIP antisense injected animals. Thus, the SCN influences the precise timing of the E(2)-induced PRL surge via VIP projections to oxytocinergic neurons of the PVN and PeVN.