Exploring androgen-regulated pathways in teleost fish using transcriptomics and proteomics.
Exploring androgen-regulated pathways in teleost fish using transcriptomics and proteomics.
复制标题
利用转录组学和蛋白质组学探索硬骨鱼中雄激素调节途径。
DOI：
10.1093/icb/ics072
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发表时间：
2012
影响因子：
2.6
通讯作者：
Denslow,NancyD
中科院分区：
文献类型：
--
作者：
Martyniuk,ChristopherJ;Denslow,NancyD
在环境中，有水生污染物干扰鱼类的雄激素信号。基于实验室和现场的实验已经利用组学技术来表征雄激素受体激动/拮抗作用的分子机制。已在鱼的卵巢和肝脏中进行了17β-群勃龙（牛饲料场周围水系统中发现的一种生长促进药物）和雄激素（如17α-甲基睾酮和17α-甲基二氢睾酮）的转录组学和蛋白质组学研究，这些鱼包括黑头呆鱼（FHM）（Pimephales promelas）、鲤鱼（Cyprinus carpio）、Qurt medaka（Oryzias latipes）和斑马鱼（Danio rerio）。在这篇简短的综述中，我们调查了最近在鱼类中的组学研究，并揭示了，尽管物种和组织的多样性，但在水生雄激素治疗中观察到了常见的细胞反应。基因本体论中反复出现的主题包括细胞凋亡、脂质的运输和氧化、激素的合成和运输、免疫反应、蛋白质代谢和细胞增殖。然而，我们还讨论了雄激素受体（AR）激活以外的其他机制，如对毒性应激的反应，雌激素受体激动，雄激素芳构化为雌激素，以及高水平的雄激素的抑制反馈机制，也可以解释鱼类的分子反应。为了进一步探索雄激素应答蛋白网络，对从暴露于17β-群勃龙的雌性FHM的肝脏收集的蛋白数据进行子网络富集分析。我们在肝脏中构建了一个假定的AR调节蛋白/细胞过程网络，包括B淋巴细胞分化、异生物质清除、低密度脂蛋白氧化、平滑肌细胞增殖和血管通透性。我们证明，蛋白质网络的建设可以提供深入了解细胞过程，可能受到雄激素的调节。
In the environment, there are aquatic pollutants that disrupt androgen signaling in fish. Laboratory and field-based experiments have utilized omics technologies to characterize the molecular mechanisms underlying androgen-receptor agonism/antagonism. Transcriptomics and proteomics studies with 17β-trenbolone, a growth-promoting pharmaceutical found in water systems surrounding cattle feed lots, and androgens such as 17α-methyltestosterone and 17α-methyldihydrotestosterone, have been conducted in ovary and liver of fish that include the fathead minnow (FHM) (Pimephales promelas), common carp (Cyprinus carpio), Qurt medaka (Oryzias latipes), and zebrafish (Danio rerio). In this mini-review, we survey recent omics studies in fish and reveal that, despite the diversity of species and tissues examined, there are common cellular responses that are observed with waterborne androgenic treatments. Recurring themes in gene ontology include apoptosis, transport and oxidation of lipids, synthesis and transport of hormones, immune response, protein metabolism, and cell proliferation. However, we also discuss other mechanisms other than androgen receptor (AR) activation, such as responses to toxicant stress, estrogen receptor agonism, aromatization of androgens into estrogens, and inhibitory feedback mechanisms by high levels of androgens that may also explain molecular responses in fish. To further explore androgen-responsive protein networks, a sub-network enrichment analysis was performed on protein data collected from the livers of female FHMs exposed to 17β-trenbolone. We construct a putative AR-regulated protein/cell process network in the liver that includes B-lymphocyte differentiation, xenobiotic clearance, low-density lipoprotein oxidation, proliferation of smooth muscle cells, and permeability of blood vessels. We demonstrate that construction of protein networks can offer insight into cell processes that are potentially regulated by androgens.