Review of the interaction between TCDD and glucocorticoids in embryonic palate
Review of the interaction between TCDD and glucocorticoids in embryonic palate
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DOI：
10.1016/0300-483x(95)03234-7
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发表时间：
1995-12-28
期刊：
影响因子：
4.5
通讯作者：
Abbott, BD
中科院分区：
文献类型：
--
作者：
Abbott, BD
2，3，7，8-四氯二苯并对二恶英(TCDD)是一种具有发育毒性和致畸作用的环境污染物。在小鼠胚胎中，TCDD可导致腭裂和肾积水。人工合成的糖皮质激素氢化可的松(HC)可诱发腭裂，在C57BL/6N胚胎小鼠中观察到TCDD和HC之间有很强的协同作用。TCDD和HC诱导的腭裂的形态和病因明显不同，HC暴露后形成小的腭裂，TCDD治疗后正常大小的腭裂未能融合。每一次接触也会改变几种生长因子的表达。当EGF、TGFGα、EGF受体和转化生长因子β被认为是一个组合的、相互作用的调节子集合时，TCDD和HC各自在该集合中产生一种独特的表达增加和/或减少的模式。HC和TCDD的相互作用导致了腭裂，其病因与HC暴露后观察到的最相似，即小的腭架。接触HC+TCDD也会产生一种生长因子的表达模式，这与HC之后看到的非常相似。TCDD和HC都通过受体介导的机制发挥作用，每种化合物都有自己的受体。AhR与TCDD结合，糖皮质激素受体(GR)与HC结合。在妊娠第14天，暴露于TCDD的胚胎腭部AhR表达下调，GR表达增加。相反，在HC暴露后，GR下调，AhR水平上升。HC+TCDD增加了这两种受体的表达，这种模式将被预测为产生HC样裂，因为GR介导的反应将导致较小的腭架。观察到的受体的交叉调节在TCDD和HC之间的协同作用中被认为是诱导腭裂的重要因素。
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces adverse biological effects including developmental toxicity and teratogenesis. In the mouse embryo, TCDD induces cleft palate and hydronephrosis. The synthetic glucocorticoid, hydrocortisone (HC), induces cleft palate and a potent, synergistic interaction has been observed between TCDD and HC in C57BL/6N embryonic mice. The morphology and etiology of TCDD- and HC-induced clefts are distinctly different with formation of small palatal shelves following HC exposure and failure of normally-sized shelves to fuse after TCDD treatment. Each exposure also alters expression of several growth factors. When EGF, TGFG alpha, EGF receptor, and the TGF beta's are considered as a combinatorial, interacting set of regulators, TCDD and HC each produce a unique pattern of increased and/or decreased expression across the set. The interaction of HC and TCDD results in a cleft palate whose etiology most closely resembles that observed after HC exposure, i.e. small palatal shelves. HC + TCDD-exposure also produces a pattern of growth factor expression which closely resembles that seen after HC. Both TCDD and HC act through receptor-mediated mechanisms and each compound has its own receptor. The Ah receptor (AhR) binds TCDD and the glucocorticoid receptor (GR) binds HC. On gestation day (GD) 14, in the embryonic palate exposed to TCDD, the AhR was downregulated and the GR expression increased. Conversely, following HC exposure, the GR was downregulated and AhR levels were elevated. HC + TCDD produced increased expression of both receptors and this pattern would be predicted to produce HC-like clefts as the GR-mediated responses would result in small palatal shelves. The observed cross-regulation of the receptors is believed to be important in the synergistic interaction between TCDD and HC for the induction of cleft palate.