Evidence that noradrenergic activity does not mediate the inhibition of luteinizing hormone secretion caused by vasoactive intestinal peptide.

We have recently shown that intracerebroventricular (i.c.v.) infusion of vasoactive intestinal peptide (VIP) in ovariectomized (OVX) rats causes a pronounced inhibition of pulsatile luteinizing hormone (LH) secretion. Since there is increasing evidence for an interaction between VIP- and norepinephrine-secreting systems in the brain, we tested the hypothesis that disruption of central noradrenergic activity would attenuate VIP-induced suppression of pulsatile LH release. Seven days prior to blood sampling, we administered either 6-hydroxydopamine (30 micrograms) or vehicle into the third cerebral ventricle of long-term OVX rats. This treatment reduced hypothalamic norepinephrine concentrations to 36% of control values. On the day of blood sampling, serial 300-microliter blood samples were taken from conscious, unrestrained animals at 5-min intervals for a total of 4 h. Each sample was replaced with an equal volume of a blood replacement mixture. Immediately following a control bleeding period of 2 h, VIP was administered i.c.v. to each animal for 2 h (at a dose of 1.8 nmol/h). The suppression of pulsatile LH secretion caused by VIP infusion was virtually identical in the 6-hydroxydopamine- and vehicle-pretreated groups. These results indicate that a substantial depletion of hypothalamic norepinephrine does not attenuate VIP-induced suppression of pulsatile LH secretion. This provides evidence that centrally administered VIP inhibits pulsatile LH secretion by a mechanism independent of noradrenergic transmission.