To identify tissues and cells that contain functionally active estrogen receptors (ERs), a transgenic mouse, ERIN (estrogen receptor action indicator), was developed that functions as a reporter of ER activity by incorporating a transgene with an estrogen responsive promoter linked to the reporter gene beta-galactosidase. Initial analysis of ERIN mice demonstrated active ER in a variety of tissues, including uterus, pituitary, and liver. The ERIN mouse will be used to aid in the identification of 1) genes regulated in individual cells where ER-ligands, both estrogens and selective estrogen receptor modulators (SERMs), exert agonist activity and 2) novel ER comodulatory proteins. By following expression of the reporter gene in the presence of ER-ligands, cells containing activated ER will be isolated using fluorescence-activated cell sorting. First, RNA will be isolated from captured cells, and cRNA will be labeled and used to probe mouse oligonucleotide gene arrays to identify fingerprints of gene expression for specific classes of ER-ligands. Second, proteins will be isolated from sorted cells and subjected to affinity chromatography using specific ER-ligand complexes as bait, followed by proteome analysis using mixed peptide sequencing to identify proteins that interact directly with ER. It is anticipated that the identification of proteins important for the cell selective actions of different ER-ligands will partially explain ER-ligand cell specificity and facilitate the identification of the next generation SERMs by screening for compounds which facilitate one class of ER-cofactor interaction over another. Before this project was initiated, my mentor and I agreed that I could carry my work with the ERIN mice forward with me to a faculty position. Consequently, I selected this project as one around which I could develop an independent career. I feel that I am halfway toward accomplishing this goal. However, an additional period of training would allow me to extend this exciting research project into the new areas of genomics and proteomics. Duke University provides an excellent research environment to further these career and research objectives in the following specific ways: 1) the applicant's mentor, Dr. McDonnell, is an accomplished and productive researcher in the area of estrogen receptor action, 2) five collaborators with expertise in genomics, proteomics, and mammalian physiology and genetics have agreed to aid in the proposed research and training program, 3) a DNA microarray core facility and other key equipment are available on the Duke University campus, and 4) a new biweekly seminar series in genomics and proteomics will provide the latest information and a forum to discuss the proposed research project.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Scientist Development Award - Research & Training (K01)
Project #
Application #
Study Section
Diabetes, Endocrinology and Metabolic Diseases B Subcommittee (DDK)
Program Officer
Hyde, James F
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Missouri-Columbia
Schools of Arts and Sciences
United States
Zip Code
Syrcle, S M; Pelch, K E; Schroder, A L et al. (2011) Altered gene expression profile in vaginal polypoid endometriosis resembles peritoneal endometriosis and is consistent with increased local estrogen production. Gynecol Obstet Invest 71:77-86
Pelch, Katherine E; Schroder, Amy L; Kimball, Paul A et al. (2010) Aberrant gene expression profile in a mouse model of endometriosis mirrors that observed in women. Fertil Steril 93:1615-1627.e18
Schroder, Amy L; Pelch, Katherine E; Nagel, Susan C (2009) Estrogen modulates expression of putative housekeeping genes in the mouse uterus. Endocrine 35:211-9
Welshons, Wade V; Nagel, Susan C; vom Saal, Frederick S (2006) Large effects from small exposures. III. Endocrine mechanisms mediating effects of bisphenol A at levels of human exposure. Endocrinology 147:S56-69
Vom Saal, Frederick S; Richter, Catherine A; Ruhlen, Rachel R et al. (2005) The importance of appropriate controls, animal feed, and animal models in interpreting results from low-dose studies of bisphenol A. Birth Defects Res A Clin Mol Teratol 73:140-5