Misztal Tomasz, Romanowicz Katarzyna, Barcikowski Bernard
Department of Endocrinology, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Science, 05-110 Jabłonna, Poland.
Anim Reprod Sci. 2004 Apr;81(3-4):245-59. doi: 10.1016/j.anireprosci.2003.08.011.
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 microg per 100 microl/h, total 400 microg). In experiment 2: (4) i.c.v. infusion of vehicle (control II); (5) i.c.v. infusion of NAL (NAL-alone, 100 microg per 100 microl/h, total 300 microg); (6) i.c.v. infusion of NAL in combination with MLT (NAL + MLT, 100 microg + 100 microg per 100 microl/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 + MLT 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.
在本研究中,我们检测了褪黑素改变由多巴胺拮抗剂(舒必利,SULP)或阿片类拮抗剂(纳洛酮,NAL)处理诱导的完整发情中期母羊促黄体生成素(LH)脉冲式分泌的能力。实验设计包括以下处理——在实验1中:(1)脑室内(i.c.v.)注入赋形剂(对照I);(2)先用SULP(0.6毫克/千克皮下注射)预处理,然后脑室内注入赋形剂(SULP + 赋形剂);(3)先用SULP预处理,然后脑室内注入褪黑素(SULP + MLT,每100微升/小时100微克,共400微克)。在实验2中:(4)脑室内注入赋形剂(对照II);(5)脑室内注入NAL(单独使用NAL,每100微升/小时100微克,共300微克);(6)脑室内注入NAL并联合MLT(NAL + MLT,每100微升/小时100微克 + 100微克)。所有注入均在下午时段进行。与对照I相比,SULP预处理使LH脉冲频率显著增加(P < 0.01),但平均LH浓度无显著变化。在SULP + MLT处理的动物中,在MLT注入期间LH浓度显著更高(P < 0.01),但这仅因一只母羊的LH分泌大幅增加所致。SULP + MLT组的显著变化发生在LH脉冲频率上。与注入期间的次数相比,在SULP + MLT组中给予褪黑素后观察到的LH脉冲次数较少(P < 0.05),且与注入赋形剂后相比也较少(P < 0.05)。与注入前相比,脑室内注入NAL使平均LH浓度显著增加(P < 0.001),且LH脉冲幅度显著增加(P < 0.01)。脑室内注入NAL后,LH分泌增强的状态也得以维持(P < 0.01),同时LH脉冲频率降低(P < 0.05)。在NAL + MLT处理的母羊中,与注入前相比,注入期间及注入后平均血浆LH浓度显著增加(P < 0.001)。在NAL + MLT组中未发现LH脉冲幅度有差异,但在同时注入两种药物期间,母羊的该参数显著高于注入赋形剂期间(P < 0.01)。LH脉冲频率有显著差异(P < 0.05),在NAL + MLT给药期间略有增加,注入后降低。总之,这些结果表明:(1)在发情中期母羊中,除多巴胺外,内源性阿片肽也参与对促性腺激素释放激素/促黄体生成素轴的抑制;(2)在长光照周期抑制的母羊中短暂给予褪黑素,在消除抑制性多巴胺输入后会抑制LH脉冲频率,但在阿片受体阻断后似乎不影响LH释放。