Serotonergic 5HT2 receptors mediate the inhibitory action of serotonin on luteinizing hormone secretion in ovariectomized, estradiol-treated ewes that are refractory to short days

Previous studies with high doses of cyproheptadine suggested that serotonergic (5HT) neural mechanisms participate in the photoperiodic inhibition of secretion of LH in ovariectomized estradiol-treated ewes. In the present study, we tested this hypothesis further with lower doses of more specific 5HT, receptor antagonists, including the highly specific ketanserin. Eight ovariectomized estradiol-treated ewes were subjected to 90 long days (16L:8D) followed by 207 short days (8L:16D) in order to induce photorefractoriness. Plasma LH concentrations were measured in blood sampled twice weekly. Changes in LH pulse frequency were measured after intrajugular injections of cyproheptadine or ketanserin (0.1, 0.25, 0.6, and 1.5 mg/kg) before the increase in LH secretion induced by the short days (SD ewes). After the ewes became refractory to short days (RSD ewes), they were again treated with the three lowest doses of cyproheptadine and ketanserin and, in addition, methysergide at the same doses. In the period following the transition from long to short photoperiod, LH secretion increased above basal levels after 42.0 +/- 0.0 days (mean +/- SEM) and then decreased after 137.0 +/- 7.4 days. In SD ewes, cyproheptadine significantly increased the number of LH pulses at the lowest dose tested (0.13 vs. 1.13 pulses/3 h at 0.1 mg/kg). Similar responses were observed at 0.25 mg/kg (0.13 vs. 0.88 pulses/3 h), at 0.6 mg/kg (0.13 vs. 0.75 pulses/3 h) and at 1.5 mg/kg (0.13 vs. 0.88 pulses/3 h). Ketanserin induced a dose-dependent increase in the number of LH pulses at 0.6 mg/kg (0 vs. 0.63 pulses/3 h) and at 1.5 mg/kg (0 vs. 0.75 pulses/3 h). In RSD ewes, the number of LH pulses was again significantly increased by cyproheptadine (0.28 vs. 1.28 pulses/3 h at 0.1 mg/kg; 0.28 vs. 1.6 pulses/3 h at 0.25 mg/kg; 0.28 vs. 1.15 pulses/3 h at 0.6 mg/kg) and by ketanserin (0.28 vs. vs. 1 pulse/3 h, at 0.1 mg/kg; 0.4 vs. 1.15 pulses/3 h, at 0.25 mg/kg: 0.28 vs. 1 pulse/3 h, at 0.6 mg/kg). With methysergide, a response was observed only at the dose of 0.6 mg/kg (0 vs. 1 pulse/3 h). The results of this study, particularly the clear responses at the lowest dose of ketanserin in RSD ewes, strongly support the hypothesis that serotonin plays a major role in the control of LH release in ovariectomized estradiol-treated ewes that are refractory to short days, and suggested that 5HT, receptors are involved in this effect.