AhR-Agonist-Induced Transcriptional Changes of Genes Involved in Thyroid Function in Primary Porcine Thyrocytes

We aimed to investigate the effects of TCDD and dioxin-like polychlorinated biphenyl 126 on the arylhydrocarbon receptor signaling pathway and on the gene expression profiles of key factors involved in thyroid function, including thyroglobulin, thyroid peroxidase, the sodium iodide symporter, Thyroid-stimulating hormone receptor, and cathepsins, using a primary porcine thyrocyte culture as the experimental model

P. Pocar; T. Klonisch; C. Brandsch; K. Eder; C. Fröhlich; C. Hoang-Vu; S. Hombach-Klonisch

2005

Scholarcy highlights

  • Dioxin-like chemicals are ubiquitously present in the environment, and the most potent isomer among the large family of dioxins and related compounds is 2,3,7,8-tetrachlorodibenzo-p-dioxin
  • We determined the effect of TCDD and polychlorinated biphenyl 126 on the gene expression profiles of key factors involved in thyroid function, including TG, thyroid peroxidase, Naþ/Iÿ symporter, Thyroid-stimulating hormone receptor, and cathepsins
  • By contrast, increased expression of cytochrome P-450 1A1 protein was only detected in thyrocytes that had been exposed to 10 nM TCDD, whereas those cultures treated with 1 nM TCDD or DMSO solvent were devoid of CYP1A1 immunobands
  • Similar to TCDD, thyrocytes responded to the dioxin-like arylhydrocarbon receptor-agonist polychlorinated biphenyls 126 with a significant increase in the expression of CYP1A1, both at mRNA and protein level
  • The two AhR agonists, TCDD and PCB 126, caused a marked induction of CYP1A1, mRNA, and protein, indicating that this cytochrome P-450 member provides a sensitive indicator for the action of dioxin-like compounds in follicular thyroid cells of the pig thyroid gland
  • TCDD and PCBs are known to alter thyroid morphology and disrupt thyroid function leading to hyperplasia of the thyroid gland and modulation of the hypothalamic-pituitary-thyroid axis
  • Both TCDD and coplanar polychlorinated biphenyl 126 significantly downregulated Naþ/Iÿ symporter and cathepsin B gene activity in porcine thyrocyte primary cultures, suggesting novel molecular mechanisms for AhRmediated actions in thyrocytes

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