Background: 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).
Objectives: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
1Receptor Biology, Reproductive and Developmental Biology Laboratory; 2Microarray and Genome Informatics Group, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA; 3Kelly Government Solutions Inc., Morrisville, North Carolina, USA; 4Cellular and Molecular Pathology Branch, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina, USA; 5Department of Chemistry, Faculty of Science, Ramkhamhaeng University, Bangkok, Thailand; 6Department of Physiology, Faculty of Science, Mahidol University, Bangkok, Thailand; 7Biostatistics Branch, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina, USA
Recommended Citation:
Sylvia C. Hewitt,1 Wipawee Winuthayanon,1 Brianna Pockette,et al. Development of Phenotypic and Transcriptional Biomarkers to Evaluate Relative Activity of Potentially Estrogenic Chemicals in Ovariectomized Mice[J]. Environmental Health Perspectives,2015-01-01,Volume 123(Issue 4):344