Abstract
Thyroid hormones (THs) play an essential role in the development of all vertebrates; in particular adequate TH content is crucial for proper neurodevelopment. TH availability and action in the brain are precisely regulated by several mechanisms, including the secretion of THs by the thyroid gland, the transport of THs to the brain and neural cells, THs activation and inactivation by the metabolic enzymes deiodinases and, in the fetus, transplacental passage of maternal THs. Although these mechanisms have been extensively studied in rats, in the last decade, models of genetically modified mice have been more frequently used to understand the role of the main proteins involved in TH signaling in health and disease. Despite this, there is little knowledge about the mechanisms underlying THs availability in the mouse brain. This mini-review article gathers information from findings in rats, and the latest findings in mice regarding the ontogeny of TH action and the sources of THs to the brain, with special focus on neurodevelopmental stages. Unraveling TH economy and action in the mouse brain may help to better understand the physiology and pathophysiology of TH signaling in brain and may contribute to addressing the neurological alterations due to hypo and hyperthyroidism and TH resistance syndromes.
Highlights
Thyroid hormones (THs) are essential for the correct development of vertebrates controlling cell growth and metabolism in all tissues
deiodinase type-2 (D2) catalyzes the conversion of T4 into the genomically active T3 while deiodinases type-3 (D3) catalyzes the deiodination of T4 and T3 into 3,3 5 -triiodo-L-thyronine and 3,3 -diiodoLthyronine (T2) respectively, inactivating TH action (Bianco and Kim, 2006)
There is a very complete study describing in detail the expression pattern of the main TH transporters in the mouse brain (Mct8, organic anion transporter family member 1c1 (Oatp1c1), L-type amino acid transporter 1, L-type amino acid transporter 2 and monocarboxylate transporter 10) from postnatal day 6 (P6) and this study revealed a precise mRNA expression pattern for each of the transporters which changed with age (Müller and Heuer, 2014)
Summary
Thyroid hormones (THs) are essential for the correct development of vertebrates controlling cell growth and metabolism in all tissues. D2 catalyzes the conversion of T4 into the genomically active T3 while D3 catalyzes the deiodination of T4 and T3 into 3,3 5 -triiodo-L-thyronine (rT3) and 3,3 -diiodoLthyronine (T2) respectively, inactivating TH action (Bianco and Kim, 2006) Another crucial step for TH action is the transport of THs across the brain barriers and the plasma membrane of target cells by TH membrane transporter proteins. Several regulatory mechanisms fine-tune the brain content of T4 and T3 These include TH secretion by the thyroid gland, TH transport to the brain and neural cells, activity of deiodinases, and in the fetus, transplacental passage of maternal THs (Obregon et al, 1984; Morreale de Escobar et al, 1990)
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