Third-ventricular infusion of neuropeptide Y suppresses luteinizing hormone secretion in ovariectomized rhesus macaques

Neuropeptide Y (NPY) has been shown to modulate gonadotropin secretion in an estrogen-dependent manner in the rat and rabbit, and to act centrally in these species to alter GnRH release. The present study examined the ability of centrally administered NPY to affect LH secretion in the primate. Human NPY (hNPY) was administered into the third cerebroventricle of unanesthetized, freely moving, ovariectomized (OVX), or estradiol (E₂)-treated OVX rhesus monkeys. LH was measured in blood samples collected remotely at 10-min intervals throughout the experiments. An extensive range of NPY doses was tested in a preliminary study in which OVX monkeys received a 3-h control infusion of Krebs Ringer phosphate buffer (KRP) followed immediately by a 3-h infusion of hNPY (0.1-50 μg/h). Only doses ≥ 5 μg/h produced a consistent and marked suppression of LH (5 μg/h; 35.1 ± 7.2% reduction, P < 0.05, n = 4). A longer duration study was performed to better characterize changes in LH pulse frequency and amplitude produced by hNPY treatment. We administered 5 μg/h and 15 μg/h to OVX (n = 5) and E₂-treated OVX (n = 4) monkeys according to the following protocol: 8 h control KRP/8-h hNPY/ 6-h recovery KRP. In OVX monkeys, LH was suppressed after 2 to 3 h of peptide infusion (P < 0.01); LH secretion returned to normal after treatment. Both doses of hNPY suppressed mean LH by approximately 55% (P < 0.05) and LH pulse frequency by ∼69% (P < 0.025). LH pulse amplitude was unaffected. In E₂-treated OVX monkeys, neither dose of hNPY affected mean LH or LH pulse amplitude. LH pulse frequency was suppressed by approximately 65% (P < 0.05) during 15-Mg/h treatment. Because centrally administered hNPY reduced LH pulse frequency and thereby mean LH levels, our results support a central, neural action of NPY to affect the GnRH/LH secretory system. The ability of estrogen feedback to alter the response to NPY treatment supports a physiological role for NPY in controlling reproduction in the primate.