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Global gene expression analysis supports a protective role for estrogen in the kidney J.W. Burt, L.D. Burgoon, T.R. Zacharewski Abstract Estrogen is a key hormonal regulator of cell growth and differentiation with diverse functions in an array of tissues. Kidney gene expression changes were examined in immature, ovariectomized C57BL/6 mice following gavage with 100 ug/kg of 17a-ethynyl estradiol (EE) or sesame oil at 2, 4, 8, 12, 18 and 24 hrs or at 72 hrs following three daily doses. An empirical Bayes analysis identified 232 differentially expressed genes using cDNA microarrays containing 13,361 mouse clones (7810 unique, annotated genes) when compared to time-matched, vehicle controls. Differentially expressed genes exhibited 6 unique k-means clusters associated with proliferation, extracellular matrix remodeling, and signaling that could be phenotypically anchored to normal kidney functions. Comparison of differentially expressed genes in the kidney, uterine, liver, mammary gland and bone indicated that EE regulates common biological processes (i.e. proliferation and xenobiotic metabolism), in addition to tissue-specific responses. Although functions associated with proliferation were represented in all tissues, each exhibited unique gene expression profiles suggesting tissue specific mechanisms of proliferation elicited by EE. Moreover, a common battery of differentially expressed genes was identified across the five tissues examined, but their temporal profiles of expression were tissue specific. Overall, these results show that EE elicits a tissue specific gene expression response in the kidney which is consistent with estrogen serving a protective role. Supplementary Data Time-course Kidney Dataset: Excel file (4.89MB) Time-course Uterus Dataset: Excel file (5.07MB) Time-course Liver Dataset: Excel file (37.5MB) Correlation Coefficients Between Kidney and Liver Gene Expression Data: Excel file (131KB) Time-course Mammary Gland Dataset: Excel file (4.65MB) Time-course Femur Dataset: Excel
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