Effects of melatonin on luteinizing hormone secretion in anestrous ewes following dopamine and opiate receptor blockade

In the present investigation we have examined the ability of melatonin to modify the pulsatile LH secretion induced by treatment with a DA antagonist (sulpiride, SULP) or opioid antagonist (naloxone, NAL) in intact mid-anestrous ewes. The experimental design comprised the following treatments—in experiment 1: (1) intracerebroventricular (i.c.v.) infusion of vehicle (control I); (2) pretreatment with SULP (0.6 mg/kg subcutaneously) and then i.c.v. infusion of vehicle (SULP+veh.); (3) pretreatment with SULP and then i.c.v. infusion of melatonin (SULP+MLT, 100 μg per 100 μl/h, total 400 μg). In experiment 2: (4) i.c.v. infusion of vehicle (control II); (5) i.c.v. infusion of NAL (NAL-alone, 100 μg per 100 μl/h, total 300 μg); (6) i.c.v. infusion of NAL in combination with MLT (NAL+MLT, 100 μg+100 μg per 100 μl/h). All infusions were performed during the afternoon hours. Pretreatment with SULP induced a significant (P<0.01) increase in LH pulse frequency, but not in mean LH concentration, compared with control I. In SULP+MLT-treated animals, the LH concentration was significantly (P<0.01) higher during MLT infusion, but due to highly increased LH secretion in only one ewe. The significant changes in the SULP+MLT group occurred in LH pulse frequency. A few LH pulses were noted after melatonin administration compared with the number during the infusion (P<0.05) and after vehicle infusion in the SULP+veh. group (P<0.05). The i.c.v. infusion of NAL evoked a significant increase in the mean LH concentration (P<0.001) and amplitude of LH pulses (P<0.01) compared with these before the infusion. The enhanced secretion of LH was also maintained after i.c.v. infusion of NAL (P<0.01) with a concomitant decrease in LH pulse frequency (P<0.05). In NAL+MLT-treated ewes, mean plasma LH concentrations increased significantly during and after the infusion compared with that noted before (P<0.001). No difference in the amplitude of LH pulses was found in the NAL+MLT group, but this parameter was significantly higher in ewes during infusion of both drugs than during infusion of the vehicle (P<0.01). The LH pulse frequency differed significantly (P<0.05), increasing slightly during NAL+MLT administration and decreasing after the infusion. In conclusion, these results demonstrate that: (1) in mid-anestrous ewes EOPs, besides DA, are involved in the inhibition of the GnRH/LH axis; (2) brief administration of melatonin in long-photoperiod-inhibited ewes suppresses LH pulse frequency after the elimination of the inhibitory DA input, but seems to not affect LH release following opiate receptor blockade.