Thyroid hormone, gene expression, and Central Nervous System: Where we are (2020)

GiseleGiannocco a,b, Marina Malta LetroKizys a, Rui MonteiroMaciel a, Janaina Sena de Souza a,c

a Departamento de Medicina, Laboratório de Endocrinologia e Medicina Translacional, Universidade Federal de São Paulo, UNIFESP/EPM, Rua Pedro de Toledo, 669 – 11 andar, São Paulo, SP 04039-032, Brazil
b Departamento de Ciências Biológicas, Universidade Federal de São Paulo, UNIFESP, Diadema, SP 09920-000, Brazil
c Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA

Abstract
Thyroid hormones (TH; T3 and T4) play a fundamental role in the fetal stage to the adult phase, controlling gene and protein expression in virtually all tissues. The endocrine and CNS systems have relevant interaction, and the TH are pivotal for the proper functioning of the CNS. A slight failure to regulate TH availability during pregnancy and/or childhood can lead to neurological disorders, for example, autism and cognitive impairment, or depression. In this review, we highlight how TH acts in controlling gene expression, its role in the CNS, and what substances widely found in the environment can cause in this tissue. We highlight the role of Endocrine Disruptors used on an everyday basis in the processing of mRNAs responsible for neurodevelopment. We conclude that TH, more precisely T3, acts mainly throughout its nuclear receptors, that the deficiency of this hormone, either due to the lack of its main substrate iodine, or by to incorrect organification of T4 and T3 in the gland, or by a mutation in transporters, receptors and deiodinases may cause mild (dysregulated mood in adulthood) to severe neurological impairment (Allan-Herndon-Dudley syndrome, presented as early as childhood); T3 is responsible for the expression of numerous CNS genes related to oxygen transport, growth factors, myelination, cell maturation. Substances present in the environment and widely used can interfere with the functioning of the thyroid gland, the action of TH, and the functioning of the CNS.
 
Keywords
Thyroid hormone Neurodevelopment BrainmRNA Receptors Endocrine disruptors

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