Nitric Oxide-Repressed Forkhead Factor FOXE1 Expression is Involved in the Inhibiton of TSH-Induced Thyroid Peroxidase Levels

MONTESINOS, MM; NICOLA, JP; NAZAR, M; PEYRET, V; LUCERO, AM; PELLIZAS, CG; MASINI-REPISO, AM

ELSEVIER IRELAND LTD

Lugar: Amsterdam; Año: 2015

hyroid 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 gen expression. In thyroid cells, TSH-stimulated nitric oxide (NO) production inhibits TSH-stimulated thyroid-specific gene expression, suggesting a potential autocrine role of NO in modulating thyroid function. Indeed, NO donors downregulates TSH-induced iodide accumulation organification in thyroid cells. Here, using FRTL-5 thyroid cells as model, we obtained insights on 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 m