Dose-related estrogen effects on gene expression in fetal mouse prostate mesenchymal cells.
Dose-related estrogen effects on gene expression in fetal mouse prostate mesenchymal cells.
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DOI：
10.1371/journal.pone.0048311
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
vom Saal FS
中科院分区：
文献类型：
--
作者：
Taylor JA;Richter CA;Suzuki A;Watanabe H;Iguchi T;Coser KR;Shioda T;vom Saal FS
小鼠胎儿在发育过程中暴露于雌激素会对前列腺形态和功能产生剂量依赖性永久性影响。胎儿前列腺间充质细胞表达雌激素受体α（ERα）和雄激素受体，并将循环雌激素和雄激素的刺激转化为旁分泌信号传导，以调节上皮细胞增殖和分化。为了深入了解不同剂量雌二醇 (E2) 在调节间充质细胞中的作用，我们检查了胎鼠前列腺间充质细胞原代培养物中 E2 诱导的转录变化。从妊娠第17天的雄性小鼠胎儿获得泌尿生殖窦间充质细胞，并在生理浓度的二氢睾酮（0.69nM）存在下暴露于10pM、100pM或100nM E2四天。基因本体论研究表明，低剂量的 E2（10 pM 和 100 pM）可诱导参与形态组织发育和甾醇生物合成的基因，但抑制参与生长因子信号传导的基因。上调和下调基因中涉及细胞粘附的基因均丰富。显示倒 U 型剂量反应的基因（在 10 pM E2 时被 E2 增强，但在 100 pM 时被抑制）在糖酵解途径中富集。在最高剂量 (100 nM) 下，E2 诱导细胞粘附、类固醇激素信号传导和代谢、细胞因子及其受体、细胞间通讯、Wnt 信号传导和 TGF-β 信号传导等基因富集。这些结果表明，当雌激素水平较低时，前列腺间充质细胞可能通过直接细胞接触来调节上皮细胞，而当雌激素水平较高时，分泌的生长因子和细胞因子可能发挥重要作用。
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 (ERα) 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 doses of E2 (10 pM and 100 pM) induce genes involved in morphological tissue development and sterol biosynthesis but suppress genes involved in growth factor signaling. Genes involved in cell adhesion were enriched among both up-regulated and down-regulated genes. Genes showing inverted-U-shape dose responses (enhanced by E2 at 10 pM E2 but suppressed at 100 pM) were enriched in the glycolytic pathway. At the highest dose (100 nM), E2 induced genes enriched for cell adhesion, steroid hormone signaling and metabolism, cytokines and their receptors, cell-to-cell communication, Wnt signaling, and TGF- β signaling. These results suggest that prostate mesenchymal cells may regulate epithelial cells through direct cell contacts when estrogen level is low whereas secreted growth factors and cytokines might play significant roles when estrogen level is high.
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DOI：
10.1046/j.1525-1373.2000.22402.x
发表时间：
2000-06-01
影响因子：
--
作者：
Gupta, C
通讯作者：
Gupta, C
影响因子：
4.8
作者：
COOKE, PS;YOUNG, P;CUNHA, GR
通讯作者：
CUNHA, GR
DOI：
10.1073/pnas.2235866100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Coser, KR;Chesnes, J;Shioda, T
通讯作者：
Shioda, T
影响因子：
7.8
作者：
CUNHA, GR;FUJII, H;REESE, BA
通讯作者：
REESE, BA
影响因子：
14.9
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.