Thyrotropin controls transcription of the thyroglobulin gene.

Heuverswyn, Brigitte Van; Streydio, Catherine; Brocas, Huguette; Refetoff, Samuel; Dumont, Jacques Emile; Vassart, Gilbert

doi:10.1073/pnas.81.19.5941

Cited by 116 publications

(54 citation statements)

References 34 publications

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“…Thyroid follicular cell differentiation and thyroid function in the adulthood are maintained by the tonic TSH stimulation from the pituitary gland (36,41,42). TSH receptor activation leads to an increase in cAMP levels that ultimately induces Tg gene expression in vivo (36,43).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Repressor DREAM Interacts with Thyroid Transcription Factor-1 and Regulates Thyroglobulin Gene Expression

Rivas

Mellström

Naranjo

et al. 2004

Journal of Biological Chemistry

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Tissue-specific gene expression depends on the interaction between tissue-specific and general transcription factors. DREAM is a Ca 2؉ -dependent transcriptional repressor widely expressed in the brain where it participates in nociception through its control of prodynorphin gene expression. In the periphery, DREAM is highly expressed in the thyroid gland, the immune system, and the reproductive organs. Here, we show that DREAM interacts with thyroid-specific transcription factor TTF-1 and regulates the expression of the thyroglobulin (Tg) gene. The mechanism also involves binding of DREAM to the thyroglobulin promoter and blockage of TTF-1-mediated transactivation. The TSH/cAMP pathway and Ca 2؉ signaling regulate DREAM-mediated transcriptional repression of the thyroglobulin gene. Furthermore, chromatin immunoprecipitation experiments in FRTL-5 cells confirmed that Tg is a bona fide target gene for DREAM transrepression in thyroid follicular cells.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Repressor DREAM Interacts with Thyroid Transcription Factor-1 and Regulates Thyroglobulin Gene Expression

Rivas

Mellström

Naranjo

et al. 2004

Journal of Biological Chemistry

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“…The nature of the other proteins whose synthesis is modified in the presence of thyrotropin (and cyclic AMP) remains to be determined. The 300000-M, product might be thyroglobulin, a protein which has been shown to be induced by thyrotropin at the genetic level [36].…”

Section: Discussionmentioning

confidence: 99%

Thyrotropin modifies the synthesis of actin and other proteins during thyroid cell culture

Passareiro

Roger

Lamy

et al. 1985

European Journal of Biochemistry

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Primary cultures of dog thyroid cells have been used to study the effects of thyrotropin on the synthesis of proteins. The cells were cultured for 4 days in serum-free and thyrotropin-free conditions. Thyrotropin was then added for varying periods of time (6-96 h). In the absence of thyrotropin, the cells have an elongated flattened aspect. Exposure to thyrotropin for 6-24 h produces retraction and rounding up of cells whereas cells incubated with thyrotropin for longer periods of time have an epithelial cuboidal shape. After varying periods of culture the cells were labelled with [35S]methionine for 6 h and then analyzed by one-and two-dimensional gel electrophoresis, followed by autoradiography. The results were as follows.1. After exposure to thyrotropin for 32 h and 48 h, the synthesis of about 18 proteins was increased while that of about 14 others was decreased. After 6 h the labelling of three and five of these proteins was already increased or decreased, respectively.2. Some of the proteins whose synthesis is modified in the presence of thyrotropin were identified. Actin synthesis was markedly decreased with a maximum 24-48 h after the addition of thyrotropin. A modification in the ratio between CI and p tubulins was also observed together with very large changes in a group of proteins having both the relative molecular mass (30000 -40000) and the isoelectric points of tropomyosins.3. Forskolin and cholera toxin caused the same qualitative and quantitative changes as thyrotropin; this suggests that the regulation by thyrotropin of the synthesis of several thyroid cell proteins is mediated by CAMP.In conclusion, the data obtained in this work might help to explain the molecular mechanisms by which thyrotropin (and CAMP) triggers the changes in cell shape which occur during thyroid cell culture. They also indicate that one of the main effects of thyrotropin takes place at the level of several proteins which belong to the cytoskeleton and which are involved in the definition of the cytostructure of the thyroid cells.The activating effect of thyroid-stimulating hormone (thyrotropin) in vivo, on both the synthesis and secretion of thyroid hormones, is associated with marked alterations in thyroid cell morphology. Acute thyrotropin administration produces an extension of pseudopod-like process of the apical cell surface into the follicular lumen (see [I] for a review). Under chronic thyrotropin deprivation the cells are flat, whereas hyperstimulation produces hyperplasia of the thyroid gland and induces 'rounded up' cuboid cells [l]. The establishment of functional primary cultures of thyroid cells 12 -41 and of normal established cell lines [5] have permitted the study of the mechanism(s) responsible for the acute changes in cell morphology. Ultramicroscopic and histoimmunological studies have led to the conclusion that acute thyrotropin administration produces a dramatic reorganization of the microfilament system [6, 71. In contrast, little attention has been devoted to the chronic (or trophic) effects of t...

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“…Experiments conducted in the rat had shown that a normal level of circulating TSH is required to sustain transcription of the Tg gene at a detectable level in the intact animal (115). This effect of TSH on the transcription of the Tg gene had also been shown to be mediated by cAMP as it could be reproduced by forskolin in the intact rat tissue incubated in vitro (116).…”

Section: Transcriptional Regulation Of Thyroid-specific Genesmentioning

confidence: 99%

The dog thyroid primary culture system: a model of the regulation of function, growth and differentiation expression by cAMP and other well-defined signaling cascades

Roger¹,

Christophe²,

Dumont³

et al. 1997

European Journal of Endocrinology

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Thyrotropin controls transcription of the thyroglobulin gene.

Cited by 116 publications

References 34 publications

Transcriptional Repressor DREAM Interacts with Thyroid Transcription Factor-1 and Regulates Thyroglobulin Gene Expression

Transcriptional Repressor DREAM Interacts with Thyroid Transcription Factor-1 and Regulates Thyroglobulin Gene Expression

Thyrotropin modifies the synthesis of actin and other proteins during thyroid cell culture

The dog thyroid primary culture system: a model of the regulation of function, growth and differentiation expression by cAMP and other well-defined signaling cascades

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