SEROTONERGIC 5HT(2)-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 sero tonergic (5HT) neural mechanisms participate in the photoperiodic inhi bition of secretion of LH in ovariectomized estradiol-treated ewes. In the present study, we tested this hypothesis further with lower doses of more specific 5HT2 receptor antagonists, including the highly spec ific ketanserin. Eight ovariectomized estradiol-treated ewes were subj ected to 90 long days (16L:8D) followed by 207 short days (8L:16D) in order to induce photorefractoriness. Plasma LH concentrations were mea sured in blood sampled twice weekly. Changes in LH pulse frequency wer e measured after intrajugular injections of cyproheptadine or ketanser in (0. 1, 0.25, 0.6, and 1.5 mg/kg) before the increase in LH secretio n induced by the short days (SD ewes). After the ewes became refractor y to short days (RSD ewes), they were again treated with the three low est doses of cyproheptadine and ketanserin and, in addition, methyserg ide at the same doses. In the period following the transition from lon g to short photoperiod, LH secretion increased above basal levels afte r 42.0 +/- 0.0 days (mean +/- SEM) and then decreased after 137.0 +/- 7.4 days. In SD ewes, cyproheptadine significantly increased the numbe r 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 inc rease 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 L H 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. 1 p ulse/3 h, at 0.1 mg/kg; 0.4 vs. 1.15 pulses/3 h, at 0.25 mg/kg: 0.28 v s. 1 pulse/3 h, at 0.6 mg/kg). With methysergide, a response was obser ved 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 ket anserin in RSD ewes, strongly support the hypothesis that serotonin pl ays a major role in the control of LH release in ovariectomized estrad iol-treated ewes that are refractory to short days, and suggested that 5HT2 receptors are involved in this effect.