title: Non-mammalian models reveal the role of alternative ligands for thyroid hormone receptors.
abstract: Thyroid hormones, or THs, are well-known regulators of a wide range of biological processes that occur throughout the lifespan of all vertebrates. THs act through genomic mechanisms mediated by thyroid hormone receptors (TRs). The main product of the thyroid gland is thyroxine or T4, which can be further transformed by different biochemical pathways to produce at least 15 active or inactive molecules. T3, a product of T4 outer-ring deiodination, has been recognized as the main bioactive TH. However, growing evidence has shown that other TH derivatives are able to bind to, and/or activate TRs, to induce thyromimetic effects. The compiled data in this review points to at least two of these TR alternative ligands: TRIAC and T2. Taking this into account, non-mammalian models have proven to be advantageous to explore new TH derivatives with potential novel actions, prompting a re-evaluation of the role and mechanism of action of TR alternative ligands that were previously believed to be inactive. The functional implications of these ligands across different vertebrates may require us to reconsider current established notions of thyroid physiology.
authors.affiliation: Instituto de Neurobiología, Departamento de Neurobiología Celular y Molecular, 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
authors.affiliation: Instituto de Neurobiología, Departamento de Neurobiología Celular y Molecular, Universidad Nacional Autónoma de México (UNAM), Boulevard Juriquilla 3001, Querétaro, Qro.76230, Mexico.
authors.forename: Iván
authors.initials: I
authors.lastname: Lazcano
authors.affiliation: Instituto de Neurobiología, Departamento de Neurobiología Celular y Molecular, 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, Departamento de Neurobiología Celular y Molecular, Universidad Nacional Autónoma de México (UNAM), Boulevard Juriquilla 3001, Querétaro, Qro.76230, Mexico.
authors.forename: Aurora
authors.initials: A
authors.lastname: Olvera
mesh_terms: D000818:Animals; D005075:Biological Evolution; D004104:Diiodothyronines / Q000378:metabolism*; D005399:Fishes / Q000145:classification / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007448:Invertebrates / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000235:genetics / Q000378:metabolism; D008024:Ligands; D010802:Phylogeny; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013045:Species Specificity; D000072637:Thyroid Epithelial Cells / Q000502:physiology*; D013974:Thyroxine / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism*
chemical_list: D004104:Diiodothyronines; D008024:Ligands; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; C010642:3,3',5-triiodothyroacetic acid; C030103:3,5-diiodothyronine; D007453:Iodide Peroxidase; D013974:Thyroxine
keywords: 3,5-Diiodothyronine; TRIAC; Thyroid hormone receptor