Neuropeptide Y (NPY) is stimulates food intake and inhibits reproduction. In the sheep, we have shown that the suppressive effect of NPY on reproduction axis is via the Y2 receptor (Y2R) (1). The present study aimed to determine whether GnRH secretion is inhibited, via the Y2R at the level of the GnRH neurosecretory terminals in the median eminence of the sheep. Firstly, dual-labelling immunohistochemistry for NPY and GnRH confirmed projections into the median eminence of the sheep brain. Secondly, to determine whether a Y2 selective ligand can inhibit GnRH secretion we injected NPY 13-36 into the median eminence of conscious ovariectomised (OVX) ewes (n=5). Injections of 1 nanomole NPY 13-36 were in 50 nanolitres 0.9% saline vehicle. Blood samples were taken from the jugular vein at 10 min intervals for 90 min prior to and following the injections of the agonist or vehicle, to measure plasma luteinizing hormone (LH) levels. This tested whether the agonist could act directly on GnRH neurosecretory terminals. The agonist caused cessation of pulsatile LH secretion and reduced mean (±SEM) LH levels from 1.7±0.23 to 1.1±0.18 (P<0.05), with no effect of vehicle. Dual label immunohistochemistry in the median eminence showed localization of the Y2R to GnRH neurosecretory terminals. In situ hybridization for the Y2R showed labelling of cells in the preoptic area of the ovine brain and studies in progress will determine the cellular localization of these receptors. These data provide strong evidence that GnRH secretion maybe inhibited by NPY, originating from the arcuate nucleus of the brain. Because the neurosecretory (external) zone of the median eminence is outside the blood-brain barrier, there is also the possibility that circulating peptide YY (Y2R ligand) from the gut may negatively regulate GnRH secretion at this level.
Reference
1- Baker-Gibb et al. (1995) J. Endocrinol. 147: 565