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

作者：Hernandez Puga Gabriela; Navarrete Ramirez Pamela; Mendoza Arturo; Olvera Aurora; Villalobos Patricia; Orozco Aurea^*

来源：Molecular and Cellular Endocrinology, 2016, 425(C): 103-110.

DOI：10.1016/j.mce.2016.01.023

• 3,5-T2
• Cortisol
• thrb
• Transrepression

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 TM beta 1 that differ by nine amino acids in the ligand-binding domain of the long-TR beta 1, whereas the short-TM beta 1 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-TM beta 1. Furthermore, 3,5-T2 and T3 down-regulate the expression of long-TR beta 1 and short-TR beta 1, 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 silica 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.

• 出版日期2016-4-15