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Objectives: Reproductive functions are influenced by various feeding regulators. Orexin, which is one of orexinergic peptides, suppresses the pulsatile secretion of luteinizing hormone (LH) in bilaterally ovariectomized (OVX) rats. However, the mechanism of this effect is still not clear. To investigate whether neuropeptide Y (NPY) is involved in the orexin A-mediated suppression of pulsatile LH secretion, we evaluated the effects of NPY antibody on the suppressive effect of orexin A., Methods: Orexin A was administered intracerebroventricularly (icv) and NPY antibody (NPY-Ab) was injected before icv administration of orexin A in OVX rats. Pulsatile LH secretion was analyzed by measuring serum LH concentrations in the next 2 h in blood samples drawn at 6-min intervals by radioimmunoassay., Results: Administration of orexin A significantly reduced the mean LH concentration and LH pulse frequency. Co-administration of NPY antibody with orexin A significantly restored the suppressive effect of orexin A on the mean LH concentration and LH pulse frequency., Conclusion: NPY mediated the suppressive effect of intracerebroventricularly injected orexin A on pulsatile LH secretion, suggesting that hypothalamic orexin suppressed pulsatile gonadotropin-releasing hormone (GnRH) secretion via NPY in the hypothalamus of female rats.

Orexins are thought to be regulatory factors of the arousal and sleep patterns. They also affect immune, feeding, autonomic and neuroendocrine systems. We have previously shown that intracerebroventricular (i.c.v.) injection of orexin decreases pulsatile luteinising hormone (LH) secretion in ovariectomised (OVX) rats. However, the details of this mechanism have not been fully examined. Intracerebroventricular injection of orexin A also stimulates corticotrophin-releasing hormone (CRH) systems, which have been implicated in the stress-induced suppression of reproductive function. In the present study, we investigated the role of CRH systems in orexin-induced LH suppression. OVX rats were implanted with i.c.v. and intravenous (i.v.) cannulae. After i.c.v. injection of orexin and/or CRH receptor antagonists, blood samples were collected through the i.v. cannula at 6-min intervals for 120 min for LH measurement. Intracerebroventricular injection of orexin A or B (3 nmol/2.5 microl) suppressed pulsatile LH secretion. Coadministration of orexin A and alpha-helical corticotrophic-releasing factor (CRF), a nonselective CRH receptor antagonist (13 nmol/2.5 microl), or astressin(2)B, a selective type2 (CRH-R2) CRH receptor antagonist (28 nmol/2.5 microl), partly restored pulsatile LH secretion. Orexin B-induced LH suppression was not restored by alpha-helical CRF. In addition, i.c.v. injection of orexin A increased CRH and urocortin II (UcnII), but not Ucn mRNA levels, in the hypothalamus. These findings suggest that CRH-R2 mediates orexin A-induced LH suppression and it is possible that CRH and UcnII in the hypothalamus are involved in this pathway.

It is well known that feeding disorders are deeply related to reproductive dysfunction, and some feeding regulatory factors may modulate the reproductive function. We examined the effect of orexins, the newly discovered orexigenic hypothalamic neuropeptides, on the pulsatile secretion of LH to clarify their influence on the reproductive function. We administered orexins or saline into the third ventricle of bilaterally ovariectomized (OVX) rats, and measured the serum LH concentration by RIA in blood samples drawn every 6 min for 2 hours to analyze the pulsatile secretion. In the orexin-treated groups, the mean LH concentration and the pulse frequency were significantly reduced (p < 0.01), but the pulse amplitude did not differ significantly. These data indicate that orexins suppress the pulsatile secretion of LH by influencing GnRH neurons at the hypothalamic level., (Copyright 1999 Academic Press.)