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核孕激素受体在鱼类大脑中的神经元和放射状胶质祖细胞中受雌激素上调。

Nuclear progesterone receptors are up-regulated by estrogens in neurons and radial glial progenitors in the brain of zebrafish.

机构信息

Neurogenesis and Oestrogens, UMR CNRS 6026, IFR140, Université de Rennes 1, Rennes, France.

出版信息

PLoS One. 2011;6(11):e28375. doi: 10.1371/journal.pone.0028375. Epub 2011 Nov 30.

Abstract

In rodents, there is increasing evidence that nuclear progesterone receptors are transiently expressed in many regions of the developing brain, notably outside the hypothalamus. This suggests that progesterone and/or its metabolites could be involved in functions not related to reproduction, particularly in neurodevelopment. In this context, the adult fish brain is of particular interest, as it exhibits constant growth and high neurogenic activity that is supported by radial glia progenitors. However, although synthesis of neuroprogestagens has been documented recently in the brain of zebrafish, information on the presence of progesterone receptors is very limited. In zebrafish, a single nuclear progesterone receptor (pgr) has been cloned and characterized. Here, we demonstrate that this pgr is widely distributed in all regions of the zebrafish brain. Interestingly, we show that Pgr is strongly expressed in radial glial cells and more weakly in neurons. Finally, we present evidence, based on quantitative PCR and immunohistochemistry, that nuclear progesterone receptor mRNA and proteins are upregulated by estrogens in the brain of adult zebrafish. These data document for the first time the finding that radial glial cells are preferential targets for peripheral progestagens and/or neuroprogestagens. Given the crucial roles of radial glial cells in adult neurogenesis, the potential effects of progestagens on their activity and the fate of daughter cells require thorough investigation.

摘要

在啮齿动物中,越来越多的证据表明核孕激素受体在发育中的大脑的许多区域中短暂表达,特别是在下丘脑之外。这表明孕激素及其代谢物可能参与与生殖无关的功能,特别是在神经发育中。在这种情况下,成年鱼类的大脑特别有趣,因为它表现出持续的生长和高度的神经发生活性,这得到了放射状胶质祖细胞的支持。然而,尽管最近已经在斑马鱼的大脑中记录了神经孕激素的合成,但关于孕激素受体存在的信息非常有限。在斑马鱼中,已经克隆并表征了一种单一的核孕激素受体(pgr)。在这里,我们证明这种 pgr 广泛分布在斑马鱼大脑的所有区域中。有趣的是,我们发现 Pgr 在放射状胶质细胞中强烈表达,而在神经元中较弱表达。最后,我们基于定量 PCR 和免疫组织化学,提供了证据表明,核孕激素受体 mRNA 和蛋白在成年斑马鱼的大脑中被雌激素上调。这些数据首次证明了放射状胶质细胞是外周孕激素和/或神经孕激素的优先靶标。鉴于放射状胶质细胞在成年神经发生中的关键作用,孕激素对其活性和子细胞命运的潜在影响需要进行彻底的研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5308/3227669/b75a02a4fde0/pone.0028375.g001.jpg

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