Mechanisms of dioxin effects on prostate development

二恶英影响前列腺发育的机制

• 批准号: 6651996
• 负责人: CATHERINE A RICHTER
• 金额: $ 4.64万
• 依托单位: UNIVERSITY OF MISSOURI-COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-15 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651996
• 关键词: androgen receptor; aromatic hydrocarbon receptor; cell growth regulation; dioxins; environmental toxicology; estrogen receptors; growth /development; growth factor; laboratory rat; male; mixed tissue /cell culture; pesticide biological effect; polymerase chain reaction; postdoctoral investigator; prostate; tissue /cell culture; transfection

DESCRIPTION (provided by applicant): This project will examine the mechanisms by which dioxin exposure disrupts development of the prostate. Dioxin toxicity is mediated by the aryl hydrocarbon receptor (AhR). Prenatal exposure to dioxin in rodents leads to a permanent decrease in prostate gland weight and permanent changes in prostatic gene expression. An understanding of the mechanisms of these effects of dioxin on prostate development could have relevance for both environmental toxicology and human prostate disease. Since the developing prostate is responsive to both androgens and estrogens, studying the role of AhR in prostate development may lead to a greater understanding of the interactions between the AhR and steroid hormone signaling pathways. In addition, study of the perturbation of prostate growth by AhR may shed light on the native roles of AhR in regulation of cell proliferation and differentiation. This study will address three hypotheses. First, the effects of dioxin on prostate development result from direct effects on prostate cells. Second, the effects of dioxin on prostate development are mediated by interactions between mesenchymal and epithelial cells. Third, the effects of dioxin on prostate development involve changes in activity and expression of androgen receptor (AR), estrogen receptor (ER), and the growth factors epidermal growth factor (EGF) and transforming growth factor beta l (TGF-beta l). These hypotheses will be tested by examination of the effects of dioxin on primary cultures of prostate cells collected from developing rats. Epithelial and mesenchymal cells will be tested separately and together using a co-culture system that allows cells to communicate chemically while remaining physically isolated. Gene expression will be measured using real time rtPCR. Activity of AhR, AR, and ER will be measured using transiently transfected reporter systems.

描述（由申请人提供）：本项目将研究机制

项目成果

Dose-related estrogen effects on gene expression in fetal mouse prostate mesenchymal cells.

• DOI: 10.1371/journal.pone.0048311
• 发表时间: 2012
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Taylor JA;Richter CA;Suzuki A;Watanabe H;Iguchi T;Coser KR;Shioda T;vom Saal FS
• 通讯作者: vom Saal FS