Hormonal control of the transcription factor Pax8 and its role in the regulation of thyroglobulin gene expression in thyroid cells

Mascia, Anna; Nitsch, Lucio; Lauro, Roberto Di; Zannini, M

doi:10.1677/joe.0.1720163

Cited by 47 publications

(27 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A primary candidate for the regulation of Pax8 mRNA expression might be TSH. In mammalian thyroid cell cultures, TSH has been shown to up-regulate Pax8 mRNA and protein expression in a cAMP-dependent manner (Fabbro et al 1998, Mascia et al 2002. Results from our X. laevis thyroid gland culture experiments are in line with these observations, since moderate increases in Pax8 mRNA were consistently detected after TSH treatment.…”

Section: Discussionsupporting

confidence: 87%

Expression of sodium-iodide symporter mRNA in the thyroid gland of Xenopus laevis tadpoles: developmental expression, effects of antithyroidal compounds, and regulation by TSH

Opitz¹,

Trubiroha²,

Lorenz³

et al. 2006

Journal of Endocrinology

View full text Add to dashboard Cite

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 semiquantitative 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 bsubunit (TSHb) 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 TSHb 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 (w20-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.

show abstract

Section: Discussionsupporting

confidence: 87%

Expression of sodium-iodide symporter mRNA in the thyroid gland of Xenopus laevis tadpoles: developmental expression, effects of antithyroidal compounds, and regulation by TSH

Opitz¹,

Trubiroha²,

Lorenz³

et al. 2006

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Interestingly, the underexpression of TG concurred with a decreased transcript level of PAX8, a member of the PAX family of transcriptional factors. PAX8 was shown to be able to activate expression of endogenous thyroid-specific genes including TG (44,45). PAX8 can also activate the promoter of TG by cooperating with thyroid transcription factor-1.…”

Section: Discussionmentioning

confidence: 99%

Molecular characterization of well-differentiated human thyroid carcinomas by cDNA arrays

Zhao

Leonard²,

Brunner³

et al. 2006

Int J Oncol

View full text Add to dashboard Cite

Abstract. Well-differentiated papillary and follicular thyroid carcinomas are the two most common types of thyroid cancer. Although cancerous cells in both types phenotypically resemble the epithelial follicular cell, the tumors display different histological characteristics and clinical outcomes. Molecular defects contributing to the separate development pathways remain largely unclear. We evaluated gene expression profiles to generate a detailed molecular characterization of the two tumor types, attempting to detect novel diagnostic and clinical markers. Gene expression profiling of 46 thyroid samples (16 papillary carcinomas, 13 follicular carcinomas and 17 normal thyroid specimens) was performed by using high-density human UniGene cDNA arrays. The identification of differentially expressed genes was based on a comparison of signal intensity ratios of tumor versus normal tissues. A cross-validation of individual filter-array hybridizations and real-time PCR analysis of selected genes were carried out to confirm data reproducibility and reliability. The majority of genes with altered expression were found in both papillary and follicular carcinomas, reflecting a close relationship between the two tumor types. However, 123 genes consisting of 45 known and 78 unknown genes were shown to be differentially expressed between papillary and follicular carcinomas. Follicular variants of papillary carcinoma, clustered together with classical papillary carcinoma, could be differentiated from follicular carcinoma. Our study revealed a set of genes differentiating follicular carcinoma from classical papillary carcinoma and follicular variant. The data generated in this study could serve as a useful source for further investigation of pathways of papillary and follicular differentiation of thyroid cancer. IntroductionThyroid cancer that originates from follicle cells of the thyroid can be subdivided into PTC, FTC and ATC (1). PTC and FTC are the two most common types of thyroid malignancies, representing approximately 80% and 15% of all thyroid cancers, respectively (2). ATC is rare, accounting for approximately 1% of thyroid cancers. PTC and FTC are well-differentiated carcinomas and bear a favorable prognosis, whereas ATC is an undifferentiated tumor and aggressive. Despite arising from the same progenitor cell, the three tumor types differ in histological features and clinical behavior. PTC is characterized by papillary growth pattern, common presence of distinctive nuclear changes and metastasis to the regional lymph nodes. In contrast, FTC is characterized by follicular architecture (lack of papillae) and invasion into the capsule and/or blood vessels. The prognosis of FTC is in general less favorable than that of PTC. ATC that is believed to occur from a terminal dedifferentiation of previously undetected long-standing papillary or follicular thyroid carcinoma (3) has a rapid progression behavior and often manifests a distant dissemination at diagnosis. The most common sites of distant spread of ATC include lung, bon...

show abstract

“…Pax8 has been hypothesized to be a link between the TSH pathway and Tg transcription. However, it has been shown that Pax8 alone is not sufficient to reactivate the expression of Tg in the absence of TSH stimulation (62).…”

Section: Tshr Signaling and Functional Differentiation Of Thyroid Cellsmentioning

confidence: 99%

Minireview: Thyrotropin Receptor Signaling in Development and Differentiation of the Thyroid Gland: Insights from Mouse Models and Human Diseases

2004

View full text Add to dashboard Cite

Hormonal control of the transcription factor Pax8 and its role in the regulation of thyroglobulin gene expression in thyroid cells

Cited by 47 publications

References 66 publications

Expression of sodium-iodide symporter mRNA in the thyroid gland of Xenopus laevis tadpoles: developmental expression, effects of antithyroidal compounds, and regulation by TSH

Expression of sodium-iodide symporter mRNA in the thyroid gland of Xenopus laevis tadpoles: developmental expression, effects of antithyroidal compounds, and regulation by TSH

Molecular characterization of well-differentiated human thyroid carcinomas by cDNA arrays

Minireview: Thyrotropin Receptor Signaling in Development and Differentiation of the Thyroid Gland: Insights from Mouse Models and Human Diseases

Contact Info

Product

Resources

About