AN INTERACTIVE PHYSIOLOGICAL-ROLE OF NEUROPEPTIDE-Y AND GALANIN IN PULSATILE PITUITARY LUTEINIZING-HORMONE SECRETION

Both neuropeptide Y (NPY) and galanin (GAL) systems have been implicat ed in the excitatory regulation of pulsatile LH secretion in the ovari ectomized rat. The present studies were designed to examine the possib le interaction of these two neuropeptides in controlling episodic LH r elease by testing the effects of central infusion:of antibodies (Ab) t o NPY and GAL, alone or in combination; additional studies tested the effects of central administration of an antisense oligodeoxynucleotide (ODN) to NPY and GAL messenger RNA. Rats were ovariectomized, implant ed with a cannula in the third ventricle, and used in experiments 2 we eks later. Central infusion, via Alter osmotic minipumps, of IgG purif ied from an NPY Ab produced a dose-related suppression of pulsatile LH secretion. Although an Ab dilution of 1:10 was ineffective, a maximal inhibitory effect was obtained using an NPY Ab dilution of 1:1, which decreased the mean levels, pulse frequency, and pulse amplitude of LH . These parameters of episodic LH secretion were also significantly re duced by central injection of antisense NPY ODN compared to those in v ehicle- or missense ODN-treated controls. Similar dose-related inhibit ory effects oh the parameters of LH Secretion were seen after central infusion of GAL Ab. Furthermore, infusion of a combination of NPY Ab a nd GAL Ab, each at the ineffective dilution of 1:10, resulted in a pro found inhibition of LH Secretion equivalent to the pattern seen with t he maximally effective 1:1 Ab dilution. These results strengthen the i dea of a physiological role for both NPY and GAL systems in the mechan ism underlying the LHRH pulse generator activity and further Suggest t hat these two excitatory neuropeptides act in concert to generate puls atile LHRH release.