ENDOGENOUS OPIOID-PEPTIDES CONTROL THE AMPLITUDE AND SHAPE OF GONADOTROPIN-RELEASING-HORMONE PULSES IN THE EWE

This study was designed to test the hypothesis that endogenous opioid peptides (EOP) mediate the negative feedback action of estradiol on Gn RH pulse size in breeding season ewes. If this hypothesis is correct, one would predict that an EOP antagonist should increase GnRH pulse si ze in estradiol-treated ovariectomized (OVX+E), but not in OVX, ewes. We, therefore, examined the effects of naloxone on GnRH pulse profiles in the hypophyseal portal blood of OVX and OVX+E ewes (n = 6/group). Samples were collected every 10 min for 6 h before, 6 h during, and 4 h after naloxone infusion. Estradiol treatment decreased GnRH pulse si ze and increased GnRH pulse frequency. Naloxone treatment had no effec t on GnRH pulse frequency, but significantly increased GnRH pulse size . However, this stimulatory action of naloxone on GnRH pulse size was evident in both OVX and OVX+E ewes. These results are thus not consist ent with the hypothesis that EOP mediate the negative feedback action of estradiol. Interestingly, naloxone not only increased GnRH pulse am plitude, but also prolonged the duration of GnRH release during a puls e. To obtain a more precise characterization of the effects of naloxon e on the dynamics of GnRH release, pulse profiles in six OVX ewes were examined in hypophyseal portal blood sampled every minute for 4 h bef ore and 4 h during naloxone infusion. Naloxone again increased both th e amplitude and duration of GnRH pulses. The increase in GnRH pulse du ration was caused by a prolongation of both the plateau and declining phases of the GnRH pulse. In addition to these effects on GnRH release during a pulse, naloxone increased the amount of GnRH collected betwe en pulses in both experiments. The stimulatory effects of naloxone on GnRH release in OVX ewes indicate that the role of EOP in the control of GnRH is not limited to mediating the feedback actions of steroids. In particular, the dramatic effects of naloxone on GnRH pulse shape an d interpulse GnRH levels raise the possibility that EOP play an import ant role in synchronizing the activity of the GnRH neurons involved in episodic GnRH secretion.