Immunoneutralization of neuropeptide Y suppresses luteinizing hormone secretion in rabbits.

ABSTRACT

In the ovarian intact rabbit, neuropeptide Y (NPY) has stimulatory actions on both LH secretion and GnRH release. The present study measured the pattern of tonic, basal LH release in the rabbit after passive immunoneutralization of endogenous NPY. Eight intact rabbits with third cerebroventricular cannulae and venous catheters were subjected to 8 h of blood sampling at 15-min intervals. Intracerebroventricular (icv) infusion of 1 ml of either normal rabbit serum (NRS) or NPY antiserum (NPY-Ab; raised in rabbits against human NPY) was begun after the second hour of basal blood sampling and was continued for the remaining 6 h of the 8-h protocol. A 1-ml matching iv dose of NRS or NPY-Ab was administered at the start of the icv infusion. All rabbits received both NRS and NPY-Ab treatments 2 weeks apart in a Latin square design. Administration of NPY-Ab significantly (P less than 0.05) suppressed plasma LH after 165 min. After 4 h, plasma LH was maximally reduced to 42% of the control value (pretreatment, 0.093 +/- 0.016 ng/ml; 4 h, 0.039 +/- 0.005 ng/ml). A reduction in the rate of pulsatile LH release also occurred during NPY-Ab treatment (P less than 0.05). Treatment with NRS had no effect on LH. The experiment was repeated in four rabbits 2 weeks after ovariectomy. Administration of NPY-Ab suppressed plasma LH after 75 min in ovariectomized (OVX) rabbits (P less than 0.05). The greatest inhibition was seen after 5 h of NPY-Ab treatment, when LH was reduced to 21% of the control level (pretreatment, 0.841 +/- 0.274 ng/ml; 5 h, 0.134 +/- 0.025 ng/ml). Both LH-pulse amplitude and frequency were suppressed in these OVX does. To determine whether central actions of NPY are of predominant importance in maintaining LH secretion, four OVX rabbits were given NPY-Ab icv only. LH was suppressed after 90 min (P less than 0.05) and was maximally inhibited after 3 h of treatment to 22% of the control value (pretreatment, 1.804 +/- 0.711 ng/ml; 3 h, 0.434 +/- 0.221 ng/ml). Although both LH-pulse amplitude and frequency were diminished, neither was decreased significantly (P greater than 0.05). FSH secretion was not affected by NRS or NPY-Ab treatment in either intact or OVX does. These results clearly indicate that in both intact and OVX does, endogenous NPY is in part responsible for maintaining basal, tonic LH secretion.(ABSTRACT TRUNCATED AT 400 WORDS)