Vasoactive intestinal peptide inhibits luteinizing hormone secretion: the inhibition is not mediated by dopamine

Vasoactive intestinal peptide (VIP) is a neuropeptide that is present in the hypothalamus and is probably a neuroendocrine regulator. The effect of VIP on pulsatile LH secretion in the long-term ovariectomized rat was re-examined in the light of earlier conflicting reports. VIP or saline was infused into the third ventricle at the rat of 15 microliters/h and blood was sampled frequently before and during the infusion. VIP at 3.5 nmol/h significantly depressed mean LH levels (p less than 0.05) and lowered pulse frequency (p less than 0.05), but had no effect on LH pulse amplitude (p greater than 0.05). VIP at lower levels was not consistently effective, and intraventricular saline was without influence. We examined indirectly whether the site of action of VIP (3.5 nmol/h) was the brain or pituitary by injecting various doses of gonadotropin-releasing hormone (GnRH; 0.5-4.0 ng/100 g BW i.v.) during VIP-induced inhibition of LH secretion and in saline-infused controls. VIP did not alter the response of the pituitary to GnRH or the slope of the GnRH-LH dose-response curve (p greater than 0.05). We conclude that the inhibitory action of VIP on pulsatile LH secretion is probably exerted in the hypothalamus. To test the hypothesis that dopamine mediates the inhibitory effects of VIP (3.5 nmol/h), animals were pretreated with the dopamine receptor blocking agent pimozide (1.26 mg/kg) in an attempt to block the actions of VIP. Pimozide did not affect the response of LH to VIP infusion (p greater than 0.05). We conclude that dopamine is not a likely mediator of the action of VIP.