The kisspeptin-GnRH pathway in human reproductive health and disease.
The kisspeptin-GnRH pathway in human reproductive health and disease.
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DOI：
10.1093/humupd/dmu009
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发表时间：
2014-07
影响因子：
13.3
通讯作者：
Anderson RA
中科院分区：
文献类型：
--
作者：
Skorupskaite K;George JT;Anderson RA
Kispeptin作为促性腺激素释放激素分泌的关键中枢调节因子的发现，使人们对人类生殖的神经内分泌调节有了新的理解。近十年来Kispeptin神经激肽B强啡肽(KNDy)通路的相关发现进一步加深了我们对内分泌、代谢和环境输入对GnRH分泌调控的理解。在这篇综述中，我们总结了目前对这些新神经肽的生理作用的了解，并讨论了这些发现的临床意义及其潜在的翻译应用。使用PubMed对截至2014年1月的所有英文文章进行系统的文献搜索。此外，还检查了所有相关原创研究文章和综述的参考文献列表。这篇综述主要集中在已发表的人类研究上，但也参考了相关的动物数据。Kispeptin是促性腺激素分泌的主要调节因子，通过这一关键作用，它对青春期的开始、性类固醇介导的反馈调节和成年生育控制至关重要。尽管在神经解剖学和功能上都存在一些性二型性，但这些功能在男性和女性身上都很明显。Kispeptin作用于GnRH的上游，在神经激肽B和强啡肽(KNDy神经肽)的旁分泌刺激和抑制输入后，直接向GnRH神经元发出信号，控制GnRH的脉动性释放。当以不同的异构体、途径和剂量给药给药时，Kispeptin强烈地刺激黄体生成素的分泌和黄体生成素的脉冲频率。目前KNDy系统的操作是翻译研究的重点，未来有可能应用于临床，以调节黄体生成素的搏动性，增加以黄体生成素搏动性降低为特征的生殖障碍的性激素分泌，包括下丘脑闭经和性腺激素减退症。相反，可能存在降低KNDy系统的活性以减少黄体生成素分泌的范围，当黄体生成素高分泌增加表型时，例如在多囊卵巢综合征中。Kispeptin是一种新近发现的神经调节剂，它控制GnRH的分泌，调节内分泌和代谢输入，调节人类生殖。对于病理性的低或高黄体生成素搏动的患者，对Kispeptin信号的操纵有可能成为新的治疗方法。
The discovery of kisspeptin as key central regulator of GnRH secretion has led to a new level of understanding of the neuroendocrine regulation of human reproduction. The related discovery of the kisspeptin-neurokinin B-dynorphin (KNDy) pathway in the last decade has further strengthened our understanding of the modulation of GnRH secretion by endocrine, metabolic and environmental inputs. In this review, we summarize current understanding of the physiological roles of these novel neuropeptides, and discuss the clinical relevance of these discoveries and their potential translational applications. A systematic literature search was performed using PUBMED for all English language articles up to January 2014. In addition, the reference lists of all relevant original research articles and reviews were examined. This review focuses mainly on published human studies but also draws on relevant animal data. Kisspeptin is a principal regulator of the secretion of gonadotrophins, and through this key role it is critical for the onset of puberty, the regulation of sex steroid-mediated feedback and the control of adult fertility. Although there is some sexual dimorphism, both neuroanatomically and functionally, these functions are apparent in both men and women. Kisspeptin acts upstream of GnRH and, following paracrine stimulatory and inhibitory inputs from neurokinin B and dynorphin (KNDy neuropeptides), signals directly to GnRH neurones to control pulsatile GnRH release. When administered to humans in different isoforms, routes and doses, kisspeptin robustly stimulates LH secretion and LH pulse frequency. Manipulation of the KNDy system is currently the focus of translational research with the possibility of future clinical application to regulate LH pulsatility, increasing gonadal sex steroid secretion in reproductive disorders characterized by decreased LH pulsatility, including hypothalamic amenorrhoea and hypogonadotropic hypogonadism. Conversely there may be scope to reduce the activity of the KNDy system to reduce LH secretion where hypersecretion of LH adds to the phenotype, such as in polycystic ovary syndrome. Kisspeptin is a recently discovered neuromodulator that controls GnRH secretion mediating endocrine and metabolic inputs to the regulation of human reproduction. Manipulation of kisspeptin signalling has the potential for novel therapies in patients with pathologically low or high LH pulsatility.
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影响因子：
56.9
作者：
BELCHETZ, PE;PLANT, TM;KNOBIL, E
通讯作者：
KNOBIL, E
DOI：
10.1073/pnas.1834399100
发表时间：
2003-09-16
影响因子：
11.1
作者：
de Roux, N;Genin, E;Milgrom, E
通讯作者：
Milgrom, E
影响因子：
56.9
作者：
Cota, D;Proulx, K;Seeley, RJ
通讯作者：
Seeley, RJ
影响因子：
4.8
作者：
Constantin, Stephanie;Caligioni, Claudia Simone;Wray, Susan
通讯作者：
Wray, Susan
影响因子：
3.3
作者：
Ciofi, P.;Leroy, D.;Tramu, G.
通讯作者：
Tramu, G.