title: 3,5-Diiodothyronine-mediated transrepression of the thyroid hormone receptor beta gene in tilapia. Insights on cross-talk between the thyroid hormone and cortisol signaling pathways.
abstract: T3 and cortisol activate or repress gene expression in virtually every vertebrate cell mainly by interacting with their nuclear hormone receptors. In contrast to the mechanisms for hormone gene activation, the mechanisms involved in gene repression remain elusive. In teleosts, the thyroid hormone receptor beta gene or thrb produces two isoforms of TRβ1 that differ by nine amino acids in the ligand-binding domain of the long-TRβ1, whereas the short-TRβ1 lacks the insert. Previous reports have shown that the genomic effects exerted by 3,5-T2, a product of T3 outer-ring deiodination, are mediated by the long-TRβ1. Furthermore, 3,5-T2 and T3 down-regulate the expression of long-TRβ1 and short-TRβ1, respectively. In contrast, cortisol has been shown to up-regulate the expression of thrb. To understand the molecular mechanisms for thrb modulation by thyroid hormones and cortisol, we used an in silico approach to identify thyroid- and cortisol-response elements within the proximal promoter of thrb from tilapia. We then characterized the identified response elements by EMSA and correlated our observations with the effects of THs and cortisol upon expression of thrb in tilapia. Our data show that 3,5-T2 represses thrb expression and impairs its up-regulation by cortisol possibly through a transrepression mechanism. We propose that for thrb down-regulation, ligands other than T3 are required to orchestrate the pleiotropic effects of thyroid hormones in vertebrates.
authors.affiliation: Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Boulevard Juriquilla 3001, Querétaro, Qro. 76230, Mexico.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Hernández-Puga
authors.affiliation: Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Boulevard Juriquilla 3001, Querétaro, Qro. 76230, Mexico.
authors.forename: Pamela
authors.initials: P
authors.lastname: Navarrete-Ramírez
authors.affiliation: Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Boulevard Juriquilla 3001, Querétaro, Qro. 76230, Mexico.
authors.forename: Arturo
authors.initials: A
authors.lastname: Mendoza
authors.affiliation: Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Boulevard Juriquilla 3001, Querétaro, Qro. 76230, Mexico.
authors.forename: Aurora
authors.initials: A
authors.lastname: Olvera
authors.affiliation: Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Boulevard Juriquilla 3001, Querétaro, Qro. 76230, Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Villalobos
authors.affiliation: Instituto de Neurobiología, Universidad Nacional Autónoma de México (UNAM), Boulevard Juriquilla 3001, Querétaro, Qro. 76230, Mexico. Electronic address: aureao@unam.mx.
authors.forename: Aurea
authors.initials: A
authors.lastname: Orozco
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004104:Diiodothyronines / Q000494:pharmacology*; D029941:Fish Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006854:Hydrocortisone / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D020218:Response Elements; D015398:Signal Transduction / Q000187:drug effects; D037042:Thyroid Hormone Receptors beta / Q000235:genetics* / Q000378:metabolism; D017210:Tilapia / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D004104:Diiodothyronines; D029941:Fish Proteins; D037042:Thyroid Hormone Receptors beta; C030103:3,5-diiodothyronine; D006854:Hydrocortisone
keywords: 3,5-T2; Cortisol; Transrepression; thrb