Central Administration of Neurokinin B Activates Kisspeptin/NKB Neurons in the Arcuate Nucleus and Stimulates Luteinizing Hormone Secretion in Ewes During the Non-Breeding Season

Central Administration of Neurokinin B Activates Kisspeptin/NKB Neurons in the Arcuate Nucleus and Stimulates Luteinizing Hormone Secretion in Ewes During the Non-Breeding Season
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DOI:
10.1262/jrd.2011-038
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发表时间:
2012-12-01
影响因子:
1.8
通讯作者:
Okamura, Hiroaki
Okamura, Hiroaki
中科院分区:
生物学3区
文献类型:
--
作者:
Sakamoto, Kohei;Murata, Ken;Okamura, Hiroaki

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人类遗传学研究表明,kisspeptin和神经激肽B(NKB)在控制促性腺激素释放激素(GnRH)分泌中起关键作用。然而,与kisspeptin相比,NKB在这种情况下的作用不太清楚。在本研究中,我们研究了在弓状核(ARC)的神经元的kisspeptin和NKB的共定位的比例,脑室内输注NKB对促黄体生成素(LH)分泌的影响,以及治疗是否激活ARC kisspeptin/NKB神经元在季节性发情母羊。免疫组织化学双标记显示,大多数kisspeptin神经元共表达NKB的ARC。将NKB输注到侧脑室中2小时引起LH的释放,这导致与盐水输注对照相比,输注开始后20至50分钟之间LH浓度显著增加。在输注结束后立即处死动物,化学染色检测ARC kisspeptin神经元中的Fos表达。NKB处理激活了整个ARC的kisspeptin神经元,大约70%的kisspeptin神经元在核的尾部表达Fos免疫反应性。本研究表明,中枢灌注NKB引起LH的放电,这是与大量的ARC kisspeptin/NKB神经元在季节性发情母羊的激活。结果提示,NKB对GnRH的脉冲性分泌具有刺激作用,ARC kisspeptin/NKB神经元群是NKB作用的部位之一。
Human genetic studies have suggested that kisspeptin and neurokinin B (NKB) play pivotal roles in the control of gonadotropin-releasing hormone (GnRH) secretion. However, the role of NKB in this context is less clear compared with that of kisspeptin. In the present study, we investigated the ratio of colocalization of kisspeptin and NKB in neurons in the arcuate nucleus (ARC), the effects of intracerebroventricular infusion of NKB on luteinizing hormone (LH) secretion and whether the treatment activates ARC kisspeptin/NKB neurons in seasonally anestrous ewes. Double-labeling immunohistochemistry revealed that the majority of kisspeptin neurons coexpressed NKB in the ARC. Infusion of NKB for 2 h into the lateral ventricle elicited a discharge of LH, which resulted in significant increases in LH concentrations between 20 and 50 min after the start of infusion compared with a saline-infused control. Animals were sacrificed immediately after the end of infusion, and Fos expression in ARC kisspeptin neurons was immunohistochemically examined. The NKB treatment activated kisspeptin neurons throughout the ARC, and approximately 70% of kisspeptin neurons expressed Fos immunoreactivity at the caudal portion of the nucleus. The present study demonstrated that a central infusion of NKB elicited a discharge of LH, which was associated with the activation of a large population of ARC kisspeptin/NKB neurons in seasonally anestrous ewes. The results suggest that NKB plays a stimulatory role in the control of pulsatile GnRH secretion and that the population of ARC kisspeptin/NKB neurons is one of sites of the NKB action in sheep.