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为什么 kisspeptin 对生殖如此重要?

Why kisspeptin is such important for reproduction?

机构信息

Department of Gynecological Endocrinology, Poznan University of Medical Sciences, Poznan, Poland.

出版信息

Gynecol Endocrinol. 2011 Jan;27(1):8-13. doi: 10.3109/09513590.2010.506291. Epub 2010 Jul 30.

Abstract

Recently discovered neuropeptide called kisspeptin is thought to be an essential gatekeeper in control of reproduction. Kisspeptin, the product of KiSS-1 gene and its G protein-coupled receptor GPR54 play a master role in the puberty period and fertility. This 54 amino acid peptide known also as metastatin, because of its metastasis suppression ability is also implicated in tumour biology. Kisspeptin/GPR54 system activates the hypothalamus-pituitary-ovarian axis. Its mechanism is not clearly understood. Kisspeptin influence is found above more at the level of hypothalamus but also at the pituitary and ovaries level. Kisspeptin can directly stimulate GnRH secretion from arcuate nucleus of hypothalamus. It is thought that kisspeptin plays an essential role in the metabolic regulation of fertility. In negative energy balance conditions an expression of KiSS-1 gene is decreased. Inactivating GPR54 mutations cause hypogonadotropic hypogonadism in humans. Simultaneously, mutations which increase GPR54 signalling are connected with gonadotropin-dependent premature puberty. Lately, possible therapeutic role of kisspeptin administration has been discussed. It was stated that kisspeptin might be used to manipulate the hypothalamic-pituitary-gonadal axis in humans. However, further studies are essential to reveal the exact mechanism and role of GPR54 agonists and antagonists applications. Moreover, the role of kisspeptin in the aspect of detection and treatment of specific cancers should be discovered.

摘要

最近发现的一种神经肽叫做 kisspeptin,被认为是控制生殖的重要守门员。Kisspeptin 是 KiSS-1 基因及其 G 蛋白偶联受体 GPR54 的产物,在青春期和生育期发挥着主导作用。这种 54 个氨基酸的肽也被称为 metastatin,因其具有抑制转移的能力,也与肿瘤生物学有关。Kisspeptin/GPR54 系统激活下丘脑-垂体-卵巢轴。其机制尚不清楚。Kisspeptin 的影响不仅在上丘脑水平,而且在下丘脑和垂体水平都被发现。Kisspeptin 可以直接刺激下丘脑弓状核 GnRH 的分泌。人们认为 kisspeptin 在生育的代谢调节中起着至关重要的作用。在负能平衡条件下,KiSS-1 基因的表达减少。GPR54 失活突变导致人类促性腺激素低下性性腺功能减退症。同时,增加 GPR54 信号的突变与促性腺激素依赖性性早熟有关。最近,人们讨论了 kisspeptin 给药的可能治疗作用。有人指出,kisspeptin 可能被用于人为地操纵人类的下丘脑-垂体-性腺轴。然而,需要进一步的研究来揭示 GPR54 激动剂和拮抗剂应用的确切机制和作用。此外,还应该发现 kisspeptin 在检测和治疗特定癌症方面的作用。

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