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197123 
Journal Article 
Review 
Review of the interaction between TCDD and glucocorticoids in embryonic palate 
Abbott, BD 
1995 
1 
Toxicology
ISSN: 0300-483X
EISSN: 1879-3185 
105 
2-3 
365-373 
English 
8571373 
WOS:A1995TQ61400032 
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, TGF 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. 
Dioxin; TCDD; Glucocorticoid; Ah receptor; Palate