Date of Award


Degree Type


Degree Name

Doctor of Philosophy


Vasoactive intestinal peptide (VIP) affects the secretion of several pituitary hormones including LH.;The initial objective was to study in greater detail the action of VIP on pulsatile LH secretion.;Ovariectomized rats were used in this study and peptide solutions were infused into the third cerebral ventricle. Venous blood was sampled every 5 min and assayed for LH.;VIP (3.5 nmole/h) lowered the mean LH levels and the pulse frequency but had no effect on pulse amplitude.;To determine whether VIP acts within the brain or at the pituitary GnRH was injected intravenously after infusion of either VIP or saline. The amplitude of the GnRH-induced LH peak was measured. VIP did not alter the sensitivity of the pituitary to GnRH; therefore VIP exerts its action within the brain.;The possibility that an endogenous VIPergic pathway may be important for influencing the action of exogenously administered VIP was examined. It was hypothesized that the destruction of VIP cell bodies in the suprachiasmatic (SCN) or the parventricular (PVN) nuclei of the hypothalamus may result in a supersensitivity to VIP. The destruction of the SCN caused animals to respond to a normally-ineffective dose of VIP (0.4 nmole/h). The destruction of the PVN did not result in an increased sensitivity to a low dose of VIP, instead it blocked the action of VIP (3.5 nmole/h). The data of both lesion experiments were interpreted to mean that a known target area of the SCN VIPergic neurons; specifically the PVN is required for the action of VIP.;Treatment of animals with either a dopamine receptor antagonist, or an opiate receptor antagonist did not block the action of VIP; therefore VIP does not exert its action via dopaminergic or opiatergic systems.;The specificity of the action of VIP was explored by examining the action of the structurally-related peptide, secretin. Secretin (3.5 nmole/h) also lowered mean LH levels and pulse frequency but VIP was slightly more potent than secretin.;VIP inhibits LH secretion by acting within the brain at the PVN.



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