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Endocrine Actions of Central Neuropeptide Y in the Ewe: Activation of the Hypothalamo‐Pituitary‐Adrenal Axis by Exogenous Neuropeptide Y and Role of Endogenous Neuropeptide Y in the Secretion of Luteinizing Hormone During the Oestrous Cycle

Neurons immunoreactive for neuropeptide Y (NPY) are abundant in the hypophysiotrophic areas of the brain. In particular, there is considerable anatomical evidence for the influence of this neuropeptide on the reproductive and hypothalamo‐pituitary‐adrenal axes. We therefore investigated whether central administration of NPY can alter the activities of the reproductive and hypothalamo‐pituitary‐adrenal axes in the ewe, and whether ovarian steroids are involved in the modulation of these events. We also attempted to investigate whether endogenous NPY is important in the control of luteinizing hormone‐releasing hormone/luteinizing hormone (LHRH/LH) secretion in the sheep oestrous cycle. Central injection of NPY (0.15 and 1.5 nmol in 50 μl saline), delivered by gravity flow into the third cerebral ventricle, had no effect on LH levels in ovariectomized (OVX) ewes (n = 6) or OVX ewes implanted with oestradiol (OVX/E2) (n = 7), nor was LH secretion altered by central NPY (1.5 nmol) in intact cycling animals in either the follicular or the luteal phase (n = 5). However, central administration of 1.5 nmol NPY to intact ewes during both the follicular (P> 0.05) and the luteal phase (P> 0.01), and in OVX/E2 ewes (P<0.5) caused a large and significant increase in plasma cortisol levels. High litre antibodies were raised to NPY in sheep and the effects of peripheral and central (intracerebroventricular) administration of anti‐NPY antibodies on the timing and/or characteristics of the E2‐induced LH surge in anoestrous ewes and of the preovulatory surge of LH in cycling ewes were determined. Intravenous administration of anti‐NPY antibodies (n = 6) had no effect on the oestradiol benzoate‐induced LH surge, compared with the control injection of non‐immune plasma (n = 6). Likewise, passive systemic immunization against NPY (n = 10) was without effect on the characteristics of the preovulatory LH surge, compared with the control group (n = 10). However, central (intracerebroventricular) administration of anti‐NPY antibodies (n = 4) delayed or abolished the preovulatory LH surge when compared with non‐immune plasma treatment in the same animals. In summary, tonic LHRH/LH secretion is unaffected by centrally administered NPY at the doses used in this study. However, the same doses of NPY activate the hypothalamo‐pituitary‐adrenal axis, thus lending clear support to the hypothesis that NPY is involved in the multifactorial regulation of adrenocorticotrophin and cortisol secretion in this species, probably by stimulating corticotrophin‐releasing hormone and/or arginine vasopressin secretion within the hypothalamus. The results of the immunization experiments further suggest that hypothalamic NPY may play a part in the modulation of the tinning of the LHRH/LH surge in the ewe. In contrast to the role of NPY in this regard in the rat, this only occurs at the level of the hypothalamus. The function of NPY in the regulation of reproduction in the sheep may therefore be to provide a means whereby the efficient generation of a preovulatory LHRH/LH surge is ensured.