Hewitt Sylvia C, Winuthayanon Wipawee, Pockette Brianna, Kerns Robnet T, Foley Julie F, Flagler Norris, Ney Elizabeth, Suksamrarn Apichart, Piyachaturawat Pawinee, Bushel Pierre R, Korach Kenneth S
Receptor Biology, Reproductive and Developmental Biology Laboratory.
Environ Health Perspect. 2015 Apr;123(4):344-52. doi: 10.1289/ehp.1307935. Epub 2015 Jan 9.
Concerns regarding potential endocrine-disrupting chemicals (EDCs) have led to a need for methods to evaluate candidate estrogenic chemicals. Our previous evaluations of two such EDCs revealed a response similar to that of estradiol (E2) at 2 hr, but a less robust response at 24 hr, similar to the short-acting estrogen estriol (E3).
Microarray analysis using tools to recognize patterns of response have been utilized in the cancer field to develop biomarker panels of transcripts for diagnosis and selection of treatments most likely to be effective. Biological effects elicited by long- versus short-acting estrogens greatly affect the risks associated with exposures; therefore, we sought to develop tools to predict the ability of chemicals to maintain estrogenic responses.
We used biological end points in uterine tissue and a signature pattern-recognizing tool that identified coexpressed transcripts to develop and test a panel of transcripts in order to classify potentially estrogenic compounds using an in vivo system. The end points used are relevant to uterine tissue, but the resulting classification of the compounds is important for other sensitive tissues and species.
We evaluated biological and transcriptional end points with proven short- and long-acting estrogens and verified the use of our approach using a phytoestrogen. With our model, we were able to classify the diarylheptanoid D3 as a short-acting estrogen.
We have developed a panel of transcripts as biomarkers which, together with biological end points, might be used to screen and evaluate potentially estrogenic chemicals and infer mode of activity.
对潜在内分泌干扰化学物质（EDC）的担忧促使人们需要评估候选雌激素化学物质的方法。我们之前对两种此类EDC的评估显示，在2小时时的反应与雌二醇（E2）相似，但在24小时时反应较弱，类似于短效雌激素雌三醇（E3）。
在癌症领域，利用能够识别反应模式的工具进行微阵列分析，以开发用于诊断和选择最可能有效的治疗方法的转录本生物标志物面板。长效和短效雌激素引发的生物学效应极大地影响了与暴露相关的风险；因此，我们试图开发工具来预测化学物质维持雌激素反应的能力。
我们使用子宫组织中的生物学终点和一种识别共表达转录本的特征模式识别工具，来开发和测试一组转录本，以便使用体内系统对潜在的雌激素化合物进行分类。所使用的终点与子宫组织相关，但化合物的最终分类对其他敏感组织和物种也很重要。
我们用已证实的短效和长效雌激素评估了生物学和转录终点，并使用一种植物雌激素验证了我们方法的有效性。利用我们的模型，我们能够将二芳基庚烷D3分类为短效雌激素。
我们已经开发了一组转录本作为生物标志物，它们与生物学终点一起，可用于筛选和评估潜在的雌激素化学物质，并推断其活性模式。
