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首页> 外文期刊>Zoological Science >GnRH as a cell proliferation regulator: mechanism of action and evolutionary implications.
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GnRH as a cell proliferation regulator: mechanism of action and evolutionary implications.

机译:GnRH作为细胞增殖调节剂:作用机理和进化意义。

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摘要

Gonadotropin-releasing hormone (GnRH) is well known as the central regulator of the reproductive system through its stimulation of gonadotropin release from the pituitary. Studies on GnRH have demonstrated that GnRH has both stimulatory and inhibitory effects on cell proliferation depending on the cell type; however, the mechanisms of these effects remain to be elucidated. Against this background we used four human cell lines, TSU-Pr1, Jurkat, HHUA and DU145, and newly found that GnRH increased or decreased the colony-formation depending on the cell line. Moreover, we demonstrated that the stimulatory and inhibitory effects of GnRH exhibit distinct ligand selectivities. In order to investigate the molecular basis of these phenomena, analyses of the expression of human GnRH receptors were performed and, moreover, the effects of GnRH were analysed under conditions in which human GnRH receptors were knocked down by the technique of RNA interference. Consequently, it was found that human type II GnRH receptor, which had been suspected of being nonfunctional because of alterations in its sequence, is involved in the effects of GnRH on cell proliferation. In this article, the influence of the autocrine activities of the cells is also reviewed, focusing on the characteristics of substances secreted from the four cell lines. Based on recent studies of GnRH and its receptors and our up-to-date findings, the evolutionary implications of GnRH action are discussed.
机译:促性腺激素释放激素(GnRH)通过刺激垂体释放促性腺激素而众所周知,是生殖系统的中央调节剂。对GnRH的研究表明,GnRH对细胞增殖具有刺激作用和抑制作用,具体取决于细胞类型。但是,这些作用的机理尚待阐明。在这种背景下,我们使用了四种人类细胞系TSU-Pr1,Jurkat,HHUA和DU145,并新发现GnRH取决于细胞系而增加或减少了集落形成。此外,我们证明了GnRH的刺激和抑制作用表现出不同的配体选择性。为了研究这些现象的分子基础,进行了人类GnRH受体表达的分析,此外,在通过RNA干扰技术敲除人类GnRH受体的条件下,分析了GnRH的作用。因此,发现人II型GnRH受体被怀疑由于其序列的改变而失去功能,参与了GnRH对细胞增殖的作用。在这篇文章中,还回顾了细胞自分泌活性的影响,重点是从这四种细胞系分泌的物质的特征。基于对GnRH及其受体的最新研究以及我们的最新发现,讨论了GnRH作用的进化意义。

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