NEUROPEPTIDE-Y SYSTEM OF THE FEMALE MONKEY HYPOTHALAMUS - RETROGRADE TRACING AND IMMUNOSTAINING

Neuropeptide Y (NPY) stimulates the release of hypothalamic gonadotrop in-releasing hormone (GnRH) as well as pituitary gonadotropins in the presence of ovarian steroids, but inhibits release in their absence. I n primates, however, the effects of NPY depend largely upon the site a nd method of administration. In ovariectomized monkeys, NPY infusion i nto the stalk-median eminence reportedly causes a dose-response increa se in GnRH secretion in the absence of gonadal steroids. To help eluci date these findings, we investigated the NPY system and its neuroendoc rine (NEU) component in the primate brain by retrograde tracing and im munostaining. One adult female and 1 juvenile female cynomolgus monkey were given microinjections of retrograde tracer into the median emine nce (ME). Two weeks later, they were perfused with fixative, and serie s of 40-mum frontal vibratome sections were collected at 500-mum inter vals through 4 mm of the forebrain. Injection sites were not visible i n the juvenile female monkey ME, so this animal served as a neurosurgi cal and injection control. Sections were immunostained using a polyclo nal NPY antiserum and the peroxidase antiperoxidase (PAP) technique. N PY immunostaining in another adult female cynomolgus monkey and in a l ate fetal female and a neonatally castrated adult male rhesus monkey g ave essentially similar results. NPY-immunoreactive (NPY-IR) neurons w ere widely distributed throughout the caudate nucleus, but appeared co ncentrated within specific hypothalamic areas. Their number, as well a s the number of NEU neurons, was nearly equal in bilaterally paired ar eas and on both sides of the hypothalamus overall. Ratios of retrograd ely labeled NPY-IR neurons to the number of NPY-IR somata were express ed as percentages of NEU NPY-IR neurons for each side and in each area . These averaged 65% in the supraoptic nucleus (SON), 41% in the parav entricular nucleus (PVN), 32% in the medial preoptic area (MPOA), whic h has only one quarter of their number of NPY-IR cells, and 11% in the medial basal hypothalamus (MBH). NPY-IR fiber densities were highest in the area olfactoria, medial septal and ventromedial nuclei. They we re high in the tuberculum olfactorium, lateral septum, nucleus accumbe ns, MPOA, PVN, dorsomedial nucleus and regions of the MBH including th e arcuate nucleus, tuber cinereum and ventral hypothalamic tract (VHT) . NPY fiber densities were moderate in the vertical portion of the dia gonal band of Broca, the ventral part of the caudate nucleus, the ante rior commissural nucleus and the lateral preoptic area, as well as the anterior and lateral hypothalamic areas, the anterior ventral periven tricular area, the suprachiasmatic nucleus and the dorsolateral SON. L astly, they were low in the nucleus and horizontal portion of the diag onal band of Broca, in the dorsal part of the caudate nucleus and in S ON. In a series of sections double-immunostained for both NPY and GnRH , we failed to find evidence of contacts or interactions between NPY- and GnRH-IR cell bodies and processes in MBH, MPOA or PVN by either li ght or electron microscopy. Our results indicate that NPY-IR neurons i n SON, PVN, MBH and to a lesser extent, in MPOA project to the ME and may perform direct hypophysiotropic functions. However, almost two thi rds of all NPY-IR neurons do not project to the ME and may participate in other, neuromodulatory roles. Together, these NPY-IR neurons contr ibute to an extensive fiber network in the monkey hypothalamus. Althou gh the NPY-IR system is partially coextensive with the GnRH-IR system, the locale and mechanism of their interactions could not be ascertain ed from our study. Whether NPY affects GnRH release directly or acts t hrough other neuronal systems in primates remains to be determined.