dose-related estrogen effects on gene expression in fetal mouse prostate mesenchymal cells剂量雌激素对胎鼠前列腺间质细胞基因表达的影响.pdfVIP

Dose-Related Estrogen Effects on Gene Expression in Fetal Mouse Prostate Mesenchymal Cells 1 1 2 2 2 Julia A. Taylor *, Catherine A. Richter , Atsuko Suzuki , Hajime Watanabe , Taisen Iguchi , 3 3 1 Kathryn R. Coser , Toshihiro Shioda , Frederick S. vom Saal 1 Division of Biological Sciences, University of Missouri, Columbia, Missouri, United States of America, 2 Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, and Department of Basic Biology, Graduate University for Advanced Studies (SOKENDAI), Aichi, Japan, 3 Molecular Profiling Laboratory, Massachusetts General Hospital Cancer Center and Harvard Medical School, Charlestown, Massachusetts, United States of America Abstract Developmental exposure of mouse fetuses to estrogens results in dose-dependent permanent effects on prostate morphology and function. Fetal prostatic mesenchyme cells express estrogen receptor alpha (ERa) and androgen receptors and convert stimuli from circulating estrogens and androgens into paracrine signaling to regulate epithelial cell proliferation and differentiation. To obtain mechanistic insight into the role of different doses of estradiol (E2) in regulating mesenchymal cells, we examined E2-induced transcriptomal changes in primary cultures of fetal mouse prostate mesenchymal cells. Urogenital sinus mesenchyme cells were obtained from male mouse fetuses at gestation day 17 and exposed to 10 pM, 100 pM or 100 nM E2 in the presence of a physiological concentration of dihydrotestosterone (0.69 nM) for four days. Gene ontology studies suggested that low dose