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 pep tide antigonadotropic decapeptide (AGD) has marked inhibitory effects on lu teinizing hormone (LH) secretion in rats and ewes. The first objective of t his study was to determine whether AGD inhibits LH secretion by regulating hypothalamic release of gonadotropin hormone (GnRH). AGD (200 mu g in 200 m u L 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 pu lses 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 t he estrous cycle and nonbreeding season. During the estrous cycle, the! eff ects of AGD on LH secretion were assessed following ovariectomy, during the metestrous, diestrous, and proestrous phases of the estrous cycle. The res ponse to AGD during the estrous cycle was compared to its effect during the anestrous season. LH, cortisol, and prolactin (PRL) concentrations were as sayed in peripheral blood samples obtained at 10-min intervals over a 6-h p eriod prior to injection of either vehicle (200 mu L of 0.3% BSA in 0.9% sa line) or AGD (200 mu g in 200 mu L 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). F urthermore, there was a significant increase (p < 0.05) in mean cortisol co ncentrations after AGD infusion in all AGD-treated groups compared to contr ols independent of season or reproductive status. PRL concentrations were a lso increased (p < 0.05) following treatment with AGD. These results sugges t that inhibition of pulsatile LH release induced by AGD is modulated by al terations in frequency of hypothalamic discharges of GnRH. Furthermore, cha nges in the inhibitory actions of AGD may contribute to the seasonal regula tion of hypothalamic GnRH secretion in the ewe.