An opioid-neuropeptide-Y transmission line to luteinizing hormone (LH)-releasing hormone neurons: a role in the induction of LH surge.

We tested the hypothesis that a decrease in hypothalamic inhibitory opioid tone produced by naloxone (NAL) will activate neuropeptide-Y (NPY) neurosecretion in 17 beta-estradiol (E2)-primed ovariectomized (ovx) rats. NPY neurosecretion was assessed in two ways. First, we studied the effects of iv saline (controls) or NAL infusion (2 mg/h) between 1100-1400 h on NPY concentrations in seven microdissected sites in the medial basal hypothalamus (MBH) and preoptic area in association with the increase in the rate of LH secretion, and then we examined the effects of NAL on the in vitro release of NPY and LHRH from the MBH of E2-primed ovx rats. We observed that in control rats, NPY concentrations in selected hypothalmic sites (median eminence, medial preoptic area, and arcuate nucleus) increased either just before LH rise at 1400 h or in association with the moderate LH surge in the afternoon. NAL infusion advanced the onset and amplified the magnitude of LH surge in the afternoon. In association with this augmentation of LH response, NAL infusion significantly increased NPY concentrations selectively in the median eminence, medial preoptic area, and arcuate nucleus. During NAL infusion at 1300 h and at the end of infusion at 1400 h, NPY concentrations in these sites increased compared to preinfusion levels at 1100 h and corresponding control levels at 1300 h. During the post-NAL infusion period until 1800 h, NPY levels remained elevated in these sites, but were not significantly different from those in control rats, which also displayed increments at this time. Further, NAL increased the in vitro efflux of both NPY and LHRH from the MBH; the increased release of two neuropeptides was dose related between 0.01-0.5 mg/ml, with the maximal increase occurring at 1.0 mg/ml NAL. Cumulatively, these studies show that 1) in association with the spontaneous LH surge in E2-primed rats, NPY concentration increased only in sites confined to the preoptic-tuberal pathway, which previously has been shown to mediate the induction of the LH surge; and 2) a decrease in the inhibitory opioid tone imposed by NAL readily augmented the hypothalamic NPY neurosecretion concomitant with an increase in duration and magnitude of the LH surge. These findings are in accord with the thesis that a decrease in the inhibitory opioid tone by the neural clock, postulated to occur before the LH surge, initiates a chain of neurosecretory events that may include a site-specific activation of NPYergic neurons.(ABSTRACT TRUNCATED AT 400 WORDS)