Environmental Protection Agency, Office Research and Development, National Exposure Research Laboratory, 26 W. Martin Luther King Drive, Cincinnati, OH 45268, USA.
Aquat Toxicol. 2011 Oct;105(3-4):618-28. doi: 10.1016/j.aquatox.2011.08.021. Epub 2011 Aug 31.
The hypothalamus-pituitary-gonadal (HPG) axis plays a central role in the maintenance of homeostasis and disruptions in its function can have important implications for reproduction and other critical biological processes. A number of compounds found in aquatic environments are known to affect the HPG axis. In the present study, we used two-dimensional electrophoresis to investigate the proteome of female and male zebrafish brain after 96 h exposure to the fungicide prochloraz. Prochloraz has known effects on a number of key HPG molecules, including antagonism of Cyp17 and Cyp19 (aromatase). Twenty-eight proteins were shown to be differentially expressed in the brains of females and 22 in males. Proteins were identified using LC-MS/MS and identities were examined relative to brain function in the context of changing steroid hormone levels. There was little overlap between sexes in proteins exhibiting differential expression. Proteins with known roles in metabolism, learning, neuroprotection, and calcium regulation were determined to be differentially regulated. Relationships between identified proteins were also examined using Ingenuity Pathway Analysis, and females were shown to exhibit enrichment of several metabolic pathways. We used differentially expressed proteins to establish a putative classifier consisting of three proteins that was able to discriminate prochloraz-exposed from control females. Putatively impacted brain functions and specific protein changes that were observed have the potential to be generalized to other that similarly impact steroid hormone levels.
下丘脑-垂体-性腺(HPG)轴在维持体内平衡方面起着核心作用,其功能的紊乱可能对生殖和其他关键的生物学过程产生重要影响。许多在水生环境中发现的化合物已知会影响 HPG 轴。在本研究中,我们使用二维电泳技术研究了在暴露于杀菌剂百菌清 96 小时后,雌性和雄性斑马鱼大脑的蛋白质组。百菌清对许多关键的 HPG 分子具有已知的影响,包括对 Cyp17 和 Cyp19(芳香酶)的拮抗作用。研究表明,在雌性大脑中,有 28 种蛋白质表达差异,在雄性大脑中则有 22 种。使用 LC-MS/MS 对蛋白质进行了鉴定,并根据类固醇激素水平变化对脑功能进行了鉴定。表现出差异表达的蛋白质在两性之间几乎没有重叠。确定了具有已知代谢、学习、神经保护和钙调节作用的蛋白质存在差异调节。还使用 Ingenuity Pathway Analysis 检查了鉴定出的蛋白质之间的关系,结果表明雌性表现出几种代谢途径的富集。我们使用差异表达的蛋白质建立了一个由三个蛋白质组成的假设分类器,该分类器能够区分暴露于百菌清的雌性和对照雌性。观察到的假定受影响的大脑功能和特定的蛋白质变化有可能推广到其他类似地影响类固醇激素水平的情况。