Discovery and evolutionary history of gonadotrophin-inhibitory hormone and kisspeptin: new key neuropeptides controlling reproduction.

Discovery and evolutionary history of gonadotrophin-inhibitory hormone and kisspeptin: new key neuropeptides controlling reproduction.
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DOI:
10.1111/j.1365-2826.2010.02018.x
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发表时间:
2010-07
影响因子:
3.2
通讯作者:
Vaudry H
Vaudry H
中科院分区:
医学3区
文献类型:
--
作者:
Tsutsui K;Bentley GE;Kriegsfeld LJ;Osugi T;Seong JY;Vaudry H

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促性腺激素释放激素(GnRH)是下丘脑中负责控制脊椎动物促性腺激素分泌的主要因子。然而,在过去的十年中,已经发现另外两种下丘脑神经肽在控制生殖功能中起关键作用:促性腺激素抑制激素(GnIH)和kisspeptin。2000年,我们在鹌鹑的下丘脑中发现了GnIH。GnIH通过对GnRH神经元和促性腺激素的作用,通过GPR 147介导,抑制鸟类促性腺激素的合成和释放。随后,在从鱼类到人类的其他脊椎动物物种中鉴定了GnIH直系同源物。与鸟类一样,哺乳动物和鱼类GnIH直系同源物抑制促性腺激素释放,表明该神经肽在控制下丘脑-垂体-性腺(HPG)轴中的保守作用。在GnIH发现后,在哺乳动物中发现了由KiSS-1基因编码的kisspeptin。与GnIH相反,kisspeptin通过GPR 54对GnRH神经元具有直接刺激作用。GPR 54也在垂体细胞中表达,但促性腺激素是否是kisspeptin的靶点仍未解决。KiSS-1基因也是高度保守的,并且已经在哺乳动物、两栖动物和鱼类中被鉴定。我们最近在几种脊椎动物中发现了KiSS-1的第二种亚型,命名为KiSS-2,但不是鸟类,啮齿动物或灵长类动物。在这篇综述中,我们强调的发现,作用机制,和功能的意义,这两个主要调节生殖轴。
Gonadotropin-releasing hormone (GnRH) is the primary hypothalamic factor responsible for the control of gonadotropin secretion in vertebrates. However, within the last decade, two other hypothalamic neuropeptides have been found to play key roles in the control of reproductive functions: gonadotropin-inhibitory hormone (GnIH) and kisspeptin. In 2000, we discovered GnIH in the quail hypothalamus. GnIH inhibits gonadotropin synthesis and release in birds through actions on GnRH neurons and gonadotropes, mediated via GPR147. Subsequently, GnIH orthologs were identified in other vertebrate species from fish to humans. As in birds, mammalian and fish GnIH orthologs inhibit gonadotropin release, indicating a conserved role for this neuropeptide in the control of the hypothalamo-pituitary-gonadal (HPG) axis across species. Following the discovery of GnIH, kisspeptin, encoded by the KiSS-1 gene, was discovered in mammals. In contrast to GnIH, kisspeptin has a direct stimulatory effect on GnRH neurons via GPR54. GPR54 is also expressed in pituitary cells, but whether gonadotropes are targets for kisspeptin remains unresolved. The KiSS-1 gene is also highly conserved and has been identified in mammals, amphibians and fish. We have recently found a second isoform of KiSS-1, designated KiSS-2, in several vertebrates, but not birds, rodents or primates. In this review, we highlight the discovery, mechanisms of action, and functional significance of these two chief regulators of the reproductive axis.
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