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

•Central Nervous System (CNS) development is under the control of thyroid hormones (TH).•TH exert that control through regulating transcriptional, posttranscriptional, and posttranslational process.•TH effects on splicing and miRNA are essential for neurogenesis, axon guidance, synapse formation alo...

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Veröffentlicht in:Seminars in cell & developmental biology 2021-06, Vol.114, p.47-56
Hauptverfasser: Giannocco, Gisele, Kizys, Marina Malta Letro, Maciel, Rui Monteiro, de Souza, Janaina Sena
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Sprache:eng
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Zusammenfassung:•Central Nervous System (CNS) development is under the control of thyroid hormones (TH).•TH exert that control through regulating transcriptional, posttranscriptional, and posttranslational process.•TH effects on splicing and miRNA are essential for neurogenesis, axon guidance, synapse formation along embryogenesis.•The imbalance on gene expression and mutations in genes related to mRNA processing are related to several neurological diseases.•Endocrine disruptors and their impact on CNS development and metabolism are alarming and a public health problem. 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.
ISSN:1084-9521
1096-3634
DOI:10.1016/j.semcdb.2020.09.007