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褪黑素是否作用于下丘脑中间基底部的多巴胺能通路,以介导光照周期对雄性绵羊催乳素分泌的影响?

Does melatonin act on dopaminergic pathways in the mediobasal hypothalamus to mediate effects of photoperiod on prolactin secretion in the ram?

作者信息

Lincoln G A, Tortonese D J

机构信息

MRC Reproductive Biology Unit, Centre for Reproductive Biology, Edinburgh, UK.

出版信息

Neuroendocrinology. 1995 Nov;62(5):425-33. doi: 10.1159/000127032.

Abstract

Previous studies have shown that the chronic administration of melatonin in the mediobasal hypothalamus (MBH) using micro-implants in Soay rams housed under long days causes a sustained decrease in the secretion of prolactin as occurs in response to short days. The purpose of this study was to investigate whether hypothalamic dopaminergic (DA) systems acting through D2 receptors may be involved in this melatonin-induced effect. Groups of Soay rams living under long days were treated in the MBH with micro-implants containing bromocriptine (BROM, DA D2 receptor agonist), or sulpiride (SULP, DA D2 receptor antagonist), given alone or in combination with melatonin (MEL), to establish whether the DA drugs would mimic or negate the effects of melatonin. A control group (C) received empty micro-implants or no treatment. The micro-implants were bilateral and were left in place for 14 weeks; the trial continued for a total of 28 weeks (14-week implant period and 14-week post-implant period) while the animals remained under long days. The ability of the micro-implants to release BROM and SULP for 14 weeks was confirmed by incubating implants in vitro and testing for the presence of the compounds using a pituitary cell bioassay. MEL in the MBH induced a marked decrease in the blood plasma concentrations of prolactin during the implant period and an increase during the postimplant period (MEL vs. C, p < 0.001). BROM given alone induced a sustained decrease in the plasma concentrations of prolactin (less marked than MEL), while SULP caused an increase (BROM and SULP vs. C, p < 0.001); the effects were restricted to the implant period. BROM given in combination with MEL produced the same effect as MEL alone during both the implant and postimplant periods, while SULP given with MEL produced the same effect as MEL during the implant period, but impaired the increase in plasma concentrations of prolactin during the postimplant period (MEL + SULP vs. MEL, p < 0.001). There were changes in growth and moulting of the pelage correlated with the marked changes in the secretion of prolactin induced by MEL, but not related to the lesser effects of BROM and SULP. In conclusion, the long-term effects of the D2 agonist and antagonist are consistent with the inhibitory role of hypothalamic DA pathways in the homeostatic regulation of prolactin secretion. The inhibitory effect of the D2 agonist did not mimic that of MEL in the MBH, thus it is unlikely that the short day MEL signal operates primarily through a hypothalamic DA system to inhibit the secretion of prolactin. However, since the administration of the D2 antagonist in the MBH did influence the response to MEL, it is probable that DA pathways are involved in relaying the effects of MEL on the long-term cycle in the secretion of prolactin in the ram.

摘要

先前的研究表明,在长日照条件下饲养的索艾羊中,通过微植入物在中基底下丘脑(MBH)长期给予褪黑素,会导致催乳素分泌持续减少,如同在短日照条件下的反应一样。本研究的目的是调查通过D2受体起作用的下丘脑多巴胺能(DA)系统是否参与这种褪黑素诱导的效应。将处于长日照条件下的索艾羊分组,在MBH中用含有溴隐亭(BROM,DA D2受体激动剂)或舒必利(SULP,DA D2受体拮抗剂)的微植入物进行处理,单独给予或与褪黑素(MEL)联合给予,以确定DA药物是否会模拟或抵消褪黑素的作用。对照组(C)接受空的微植入物或不进行处理。微植入物是双侧的,放置14周;试验总共持续28周(14周的植入期和14周的植入后期),在此期间动物一直处于长日照条件下。通过在体外孵育植入物并使用垂体细胞生物测定法检测化合物的存在,证实了微植入物释放BROM和SULP达14周的能力。MBH中的MEL在植入期导致血浆催乳素浓度显著降低,在植入后期升高(MEL与C相比,p < 0.001)。单独给予BROM导致血浆催乳素浓度持续降低(不如MEL明显),而SULP则导致升高(BROM和SULP与C相比,p < 0.001);这些效应仅限于植入期。BROM与MEL联合给予在植入期和植入后期产生的效果与单独给予MEL相同,而SULP与MEL联合给予在植入期产生的效果与MEL相同,但在植入后期损害了血浆催乳素浓度的升高(MEL + SULP与MEL相比,p < 0.001)。被毛的生长和换毛发生了变化,这与MEL诱导的催乳素分泌的显著变化相关,但与BROM和SULP的较小效应无关。总之,D2激动剂和拮抗剂的长期效应与下丘脑DA途径在催乳素分泌稳态调节中的抑制作用一致。D2激动剂在MBH中的抑制作用并未模拟MEL的作用,因此短日照MEL信号不太可能主要通过下丘脑DA系统来抑制催乳素的分泌。然而,由于在MBH中给予D2拮抗剂确实影响了对MEL的反应,DA途径很可能参与传递MEL对公羊催乳素分泌长期周期的影响。

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