CHANGES IN PULSATILE RELEASE OF NEUROPEPTIDE-Y AND LUTEINIZING-HORMONE (LH)-RELEASING HORMONE DURING THE PROGESTERONE-INDUCED LH SURGE IN RHESUS-MONKEYS

In previous studies we have shown that the pulsatility of LH-releasing hormone (LHRH) release in gonadectomized monkeys is modulated by inpu t from neuropeptide-Y (NPY) neurons: 1) the endogenous release of NPY in the stalk-median eminence (S-ME) was pulsatile; 2) NPY pulses were temporally correlated with LHRH pulses, with NPY pulses preceding LHRH pulses by approximately 5 min; and 3) infusion of NPY into the S-ME s timulated LHRH release, whereas 4) infusion of antiserum to NPY suppre ssed endogenous LHRH pulses. It is not known, however, whether ovarian steroid hormones alter the pulsatility of NPY and LHRH release or whe ther the temporal correlation of NPY and LHRH pulses is maintained dur ing the LH surge. In the present study we examined the changes in puls atile release of NPY and LHRH in ovariectomized monkeys treated with e stradiol benzoate (EB) followed by progesterone or oil. Using push-pul l perfusion, perfusate samples from S-ME were collected at 10-min inte rvals for 15 h. NPY and LHRH concentrations in the perfusates were mea sured by RIA. Circulating LH levels were also monitored by periodic bl ood sampling and RIA. Injection of progesterone (sc) after EB induced an LH surge with a peak latency of 7.3 +/- 1.3 h (mean +/- SE) in seve n of seven monkeys, whereas oil injection after EB elicited an LH surg e in none of seven monkeys. The progesterone-induced LH surge was asso ciated with an increase in LHRH release; the mean, pulse amplitude, an d pulse frequency increased significantly (for all, P < 0.05) 4-8 h af ter progesterone. NPY pulse frequency also increased significantly (P < 0.05) 4-8 h after progesterone treatment, whereas mean release and p ulse amplitude did not change in response to progesterone. Oil treatme nt after EB administration did not alter any parameter of LHRH and NPY pulses. Interestingly, the NPY and LHRH pulses were highly correlated (P < 0.001) in monkeys treated with either EB-progesterone or EB-oil, and NPY pulses preceded LHRH pubes by 4.8 +/- 0.7 and 5.1 +/- 0.6 min , respectively. In summary, 1) an episode of increased LHRH release oc curs before and during the progesterone-induced LH surge; 2) accelerat ion of LHRH pulse frequency and the increase in LHRH pulse amplitude a fter progesterone are accompanied by acceleration of NPY pulse frequen cy; and 3) ovarian steroids do not affect the temporal correlation bet ween NPY and LHRH pulses. These results suggest that modulation of NPY pulse frequency by ovarian steroids may be a signal to stimulate LHRH pulses during the progesterone-induced LH surge. Collectively, these data suggest that NPY neurons play an important role in the modulation of LHRH pulsatility and in the feedback effects of ovarian steroids.