Inhibition of hypothalamic GnRH secretion in the ewe by antigonadotropic decapeptide during the estrous cycle and nonbreeding season

Previous experiments from our laboratory and others have shown that the peptide antigonadotropic decapeptide (AGD) has marked inhibitory effects on luteinizing hormone (LH) secretion in rats and ewes. The first objective of this study was to determine whether AGD inhibits LH secretion by regulating hypothalamic release of gonadotropin hormone (GnRH). AGD (200 μg in 200 μL of 0.3% bovine serum albumin [BSA] saline) or vehicle was infused into the lateral ventricle of ovariectomized (OVX) ewes with hypophyseal-portal cannulae, and GnRH secretion was monitored. The frequency of GnRH and LH pulses in AGD-treated ewes was significantly decreased (p<0.05) but did not change in the control ewes. The second objective of this investigation was to evaluate changes in hypothalamic sensitivity to AGD in the ewe during the estrous cycle and nonbreeding season. During the estrous cycle, the effects of AGD on LH secretion were assessed following ovariectomy, during the metestrous, diestrous, and proestrous phases of the estrous cycle. The response to AGD during the estrous cycle was compared to its effect during the anestrous season. LH, cortisol, and prolactin (PRL) concentrations were assayed in peripheral blood samples obtained at 10-min intervals over a 6-h period prior to injection of either vehicle (200 μL of 0.3% BSA in 0.9% saline) or AGD (200 μg in 200 μL of vehicle), and for an additional 10 h following treatment. LH pulse frequency decreased after treatment with AGD (p<0.05) at all times in OVX and intact ewes compared to vehicle-treated controls. During the anestrous season, AGD treatment was more effective in inhibiting LH pulse frequency than during the breeding season (p<0.05). Furthermore, there was a significant increase (p<0.05) in mean cortisol concentrations after AGD infusion in all AGD-treated groups compared to controls independent of season or reproductive status. PRL concentrations were also increased (p<0.05) following treatment with AGD. These results suggest that inhibition of pulsatile LH release induced by AGD is modulated by alterations in frequency of hypothalamic discharges of GnRH. Furthermore, changes in the inhibitory actions of AGD may contribute to the seasonal regulation of hypothalamic GnRH secretion in the ewe.