Role of neuropeptide-Y in episodic luteinizing hormone release in ovariectomized rats: an excitatory component and opioid involvement.

Abstract

We tested the hypothesis that hypothalamic neuropeptide-Y (NPY) is an excitatory signal in the episodic secretion of LH in ovariectomized (ovx) rats and that the suppression of LH secretion that consistently follows intracerebroventricular administration of NPY is due to concurrent release of opioids or CRH, both previously shown to readily inhibit LH release. In the first experiment, ovx rats received continuous intraventricular infusion of either serum containing NPY antibodies (NPY-Ab) or normal rabbit serum (control) at dilutions of 1:5 or 1:1. NPY-Ab infusion at a 1:5 dilution significantly decreased mean plasma LH levels and LH pulse amplitude without affecting LH pulse frequency over a 3-h period of observation. However, infusion of relatively more concentrated NPY-Ab (1:1) markedly decreased not only mean plasma LH levels and LH pulse amplitude, but also the frequency of LH episodes. In the next experiment, we observed that intraventricular administration of NPY (0.2 nmol) suppressed LH release for 60 min. However, blockade of opiate receptors with iv infusion of naloxone (2 mg/h) before and after NPY injection completely counteracted the NPY-induced inhibition of LH release. On the other hand, prior blockade of the CRH receptors with alpha-helical CRH-(9-41) (25 or 100 micrograms/rat) was ineffective in reversing the inhibitory LH response of NPY (0.125 nmol). These results together with our previous demonstration of morphological communication between NPY and beta-endorphin neurons, show that suppression of LH by exogenous NPY in ovx rats may result from concurrent stimulation of opioids, primarily beta-endorphin. However, diminution of all parameters of episodic LH secretion by NPY-Ab affirms the notion that the NPY network is a physiologically important excitatory component of the hypothalamic pulse generator circuitry that regulates episodic LH secretion in rats.