Nitric oxide-repressed Forkhead factor FoxE1 expression is involved in the inhibition of TSH-induced thyroid peroxidase levels
| Autor: | Claudia Gabriela Pellizas, Magalí Nazar, Ana María Masini-Repiso, Ariel Maximiliano Lucero, María del Mar Montesinos, Juan Pablo Nicola, Victoria Peyret |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
endocrine system medicine.medical_specialty Transcription Genetic endocrine system diseases medicine.medical_treatment Down-Regulation Thyrotropin Nitric Oxide Iodide Peroxidase Biochemistry Gene Expression Regulation Enzymologic Cell Line Thyroid hormone receptor beta 03 medical and health sciences Endocrinology Thyroid peroxidase Internal medicine Cyclic AMP Cyclic GMP-Dependent Protein Kinases medicine Animals Nitric Oxide Donors Promoter Regions Genetic Cyclic GMP Molecular Biology Nitrites Thyroid hormone receptor biology Chemistry Forkhead Transcription Factors Organification Rats 030104 developmental biology biology.protein Cattle Thyroglobulin Thyroid function Signal transduction Protein Binding Signal Transduction Hormone |
| Zdroj: | Molecular and Cellular Endocrinology. 420:105-115 |
| ISSN: | 0303-7207 |
| Popis: | Thyroid peroxidase (TPO) is essential for thyroid hormone synthesis mediating the covalent incorporation of iodine into tyrosine residues of thyroglobulin process known as organification. Thyroid-stimulating hormone (TSH) via cAMP signaling is the main hormonal regulator of TPO gene expression. In thyroid cells, TSH-stimulated nitric oxide (NO) production inhibits TSH-induced thyroid-specific gene expression, suggesting a potential autocrine role of NO in modulating thyroid function. Indeed, NO donors downregulate TSH-induced iodide accumulation and organification in thyroid cells. Here, using FRTL-5 thyroid cells as model, we obtained insights into the molecular mechanism underlying the inhibitory effects of NO on iodide organification. We demonstrated that NO donors inhibited TSH-stimulated TPO expression by inducing a cyclic guanosine monophosphate-dependent protein kinase-mediated transcriptional repression of the TPO gene. Moreover, we characterized the FoxE1 binding site Z as mediator of the NO-inhibited TPO expression. Mechanistically, we demonstrated that NO decreases TSH-induced FoxE1 expression, thus repressing the transcripcional activation of TPO gene. Taken together, we provide novel evidence reinforcing the inhibitory role of NO on thyroid cell function, an observation of potential pathophysiological relevance associated with human thyroid pathologies that come along with changes in the NO production. |
| Databáze: | OpenAIRE |
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