A POSSIBLE ROLE OF NEUROPEPTIDE-Y IN THE CONTROL OF THE ONSET OF PUBERTY IN FEMALE RHESUS-MONKEYS

The onset of puberty is heralded by an increase in pulsatile LHRH rele ase. Since neuropeptide Y (NPY) has been implicated as a major regulat or in the control of pulsatile LHRH release in mature monkeys, we have hypothesized that maturational changes in the NPY neuronal system pla y an important role in puberty. To test this hypothesis, three experim ents were conducted in female rhesus monkeys using a push-pull perfusi on method. In the first experiment, changes in NPY release in the stal k-median eminence (S-ME) during puberty were determined in 9 prepubert al, 7 early pubertal and 8 midpubertal monkeys. NPY and LHRH levels we re measured in aliquots of the same perfusate samples obtained from th e S-ME. NPY release was pulsatile in all three groups. Mean NPY releas e and pulse frequency increased significantly from the prepubertal thr ough the midpubertal stage. These developmental changes in NPY release were parallel to those observed for LHRH release in the same monkeys. In order to examine whether NPY infusion into the S-ME influences LHR H release during puberty, in the second experiment, NPY (10(-6) or 10( -8) M) or vehicle was infused into the S-ME for 10 min at 90-min inter vals in 5 prepubertal and 9 midpubertal monkeys. In the midpubertal st age, infusion of NPY at doses of 10(-8) and 10(-6) M resulted in signi ficant (p < 0.01) increases in LHRH release, while vehicle administrat ion had no effect. In contrast, in prepubertal monkeys, neither NPY no r vehicle infusion altered LHRH release. In order to test whether endo genous NPY plays a role in the maintenance of pulsatile LHRH release, in the third experiment, a specific antiserum to NPY (aNPY) was infuse d into the S-ME of 6 prepubertal and 8 midpubertal monkeys. Infusion o f aNPY (1:100, 1:1,000 dilution) significantly suppressed LHRH release in midpubertal but not prepubertal monkeys. The results are summarize d as follows. (1) In prepubertal monkeys, NPY release is low, and the presence of NPY in the S-ME does not influence LHRH release. (2) At th e onset of puberty, NPY release begins to increase, and NPY probably s tarts to stimulate LHRH release. (3) In the midpubertal period, NPY re lease increases further, and NPY in the S-ME is highly stimulatory to LHRH release. (4) Immunoneutralization of endogenous NPY suppresses pu lsatile LHRH release during the midpubertal period but not the prepube rtal period, suggesting that a developmental change in the sensitivity of the LHRH neurosecretory system to NPY occurs sometime after the on set of puberty, and that endogenous NPY is important for pulsatile LHR H release during puberty. It is concluded that the regulation of LHRH release by NPY is a contributing factor for the onset of puberty in fe male rhesus monkeys.