Vasoactive Intestinal Polypeptide Effects a Central Inhibition of Pulsatile Luteinizing Hormone Secretion in Ovariectomized Rats*

Abstract

Recent studies implicate vasoactive intestinal polypeptide (VIP) as a neurotransmitter or neuromodulator, and several observations suggest that VIP, originating within the brain, may alter the secretion of GnRH. We have tested the hypothesis that VIP acts as a central nervous system regulator of pulsatile GnRH secretion, as reflected in pulsatile LH release, by assessing the effect of intraventricularly administered VIP on several parameters of LH secretion in ovariectomized (OVX) rats. To examine the possibility that centrally administered VIP alters pituitary responsiveness to GnRH, we challenged OVX rats with GnRH and compared the LH response in VIP-treated animals with that in control animals. Finally, we tested the hypothesis that exposure of the animal to gonadal steroids alters VIPs effect on LH secretion by assessing LH release during central administration of VIP in OVX rats pretreated with estrogen and progesterone. Unanesthetized rats with external jugular cannulae were bled at 5-min intervals for 2 h before infusion and for 2 h during continuous intraventricular infusion of either VIP (1.8 nmol/h) or saline. Blood samples (300 or 400 .mu.l) were replaced with an equal volume of a blood replacement mixture. VIP infusion significantly reduced LH pulse frequency by 80% (P < 0.002) and mean LH levels by 60% (P < 0.002), but did not significantly affect LH pulse amplitude. In contrast, saline infusion produced no significant change in any of these parameters. The plasma LH response to 2 ng GnRH, iv, in VIP-treated animals did not differ significantly from that in control animals. Finally, VIP infusion had no discernible effect on LH secretion in OVX rats pretreated with estradiol benzoate (50 .mu.g) and progesterone (25 mg). These results demonstrate that VIP can profoundly inhibit pulsatile LH secretion in the OVX rat and provide evidence to suggest that this effect is not due to diminished pituitary responsiveness to GnRH. Based upon these observations, we argue that VIP, originating within the brain, may be an important inhibitory regulator of pulsatile GnRH secretion.