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Journal of Endocrinology (2006) 190, 157-170       DOI: 10.1677/joe.1.06606
© 2006 Society for Endocrinology
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Expression of sodium-iodide symporter mRNA in the thyroid gland of Xenopus laevis tadpoles: developmental expression, effects of antithyroidal compounds, and regulation by TSH

Robert Opitz, Achim Trubiroha, Claudia Lorenz, Ilka Lutz, Sabine Hartmann1, Tobias Blank1, Thomas Braunbeck1 and Werner Kloas2

Department of Inland Fisheries, Leibniz-Institute of Freshwater Ecology and Inland Fisheries, Mueggelseedamm 310, D-12587 Berlin, Germany
1 Aquatic Ecology and Toxicology, Department of Zoology, University of Heidelberg, D-69120 Heidelberg, Germany
2 Department of Endocrinology, Institute of Biology, Humboldt University, D-10115 Berlin, Germany

(Requests for offprints should be addressed to W Kloas; Email: werner.kloas{at}igb-berlin.de)

The uptake of iodide represents the first step in thyroid hormone synthesis by thyroid follicular cells and is mediated by the sodium-iodide symporter (NIS). In mammals, expression of NIS is stimulated by TSH and transcription of the NIS gene involves regulation by the thyroid-specific transcription factors Pax8 and Nkx2.1. In this study, we examined the mRNA expression of NIS, Pax8 and Nkx2.1 in the thyroid gland of Xenopus laevis tadpoles by semi-quantitative reverse transcriptase (RT)-PCR. During spontaneous metamorphosis, NIS mRNA expression was low in premetamorphic tadpoles, increased throughout prometamorphosis, and peaked at climax stage 60. Analysis of TSH ß-subunit (TSHß) mRNA in the pituitary of the same tadpoles revealed a close temporal relationship in the expression of the two genes during metamorphosis, suggesting a regulatory role of TSH in the developmental expression of NIS. Treatment of tadpoles with goitrogenic compounds (sodium perchlorate and ethylenethiourea) increased TSHß mRNA expression (approximately twofold) and caused thyroid gland hyperplasia, confirming that feedback along the pituitary–thyroid axis was operative. Analysis of gene expression in the thyroid gland revealed that goitrogen treatment was correlated with increased expression of NIS mRNA (~20-fold). In the thyroid gland organ culture experiments, bovine TSH (bTSH; 1 mU/ml) strongly induced NIS mRNA expression. This effect was mimicked by co-culture of thyroid glands with pituitaries from stage 58 tadpoles and by agents that increase intracellular cAMP (forskolin, dibutyryl-cAMP). In addition, it could be shown that thyroid glands of X. laevis tadpoles express Pax8 and Nkx2.1 mRNA in a developmentally regulated manner and that ex vivo treatment of thyroid glands with bTSH, forskolin, and cAMP analogs increased the expression of Pax8 and Nkx2.1 mRNA. This is the first report on developmental profiles and hormonal regulation of thyroid gland gene expression in amphibian tadpoles and, together, results reveal a critical role of TSH in the regulation of NIS mRNA expression in the thyroid gland of X. laevis tadpoles.




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M. G. Baratta, I. Porreca, and R. Di Lauro
Oncogenic Ras Blocks the cAMP Pathway and Dedifferentiates Thyroid Cells Via an Impairment of Pax8 Transcriptional Activity
Mol. Endocrinol., June 1, 2009; 23(6): 838 - 848.
[Abstract] [Full Text] [PDF]




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