Regulation of thyroid hormone bioactivity by deiodinases; from invertebrates to humans

Abstract

Event Abstract Back to Event Regulation of thyroid hormone bioactivity by deiodinases; from invertebrates to humans Theo J. Visser1* 1 Erasmus University Medical Center, Internal Medicine, Netherlands In most species, the thyroid largely secretes the prohormone T4 and a small amount of the bioactive hormone T3. Most T3 is generated by outer ring deiodination (ORD) of T4. T4 is inactivated by inner ring deiodination (IRD) to rT3, and T3 by IRD to 3,3’-T2. In mammals, 3 deiodinases are involved in these processes. D1 is highly expressed in liver and kidneys and has both ORD and IRD activities. It is important for production of serum T3. D2 has only ORD activity; it is highly expressed in brain, pituitary and brown adipose tissue, where it plays an important role in local T3 production. D3 has only IRD activity and is highly expressed in fetal tissues (e.g. brain), placenta and pregnant uterus, and in adult brain and skin. With D2, D3 is crucial for local regulation of thyroid hormone (TH) bioactivity in the brain, and thus for brain development. In all vertebrates, the deiodinases are homologous selenoproteins, containing a selenocysteine (Sec) residue in the active center. Most fish have 2 closely related D3 genes, D3a and D3b, the purpose of which is unknown. In addition to deiodination, TH is metabolized by conjugation with glucuronic acid or sulfate and by side chain modification. The latter produces, among others, the acetic acid metabolites Tetrac (TA4) and Triac (TA3). Interestingly, TA3 has equal or even higher affinity for the T3 receptors TRα and TRβ, respectively. TH is essential for metamorphosis in different species, including fish, amphibians and invertebrates such as ascidians and amphioxus. We have recently characterized a deiodinase from Branchiostoma floridae, with remarkable properties. Firstly, this deiodinase, termed bfDy, is not a selenoprotein but features a Cys residue instead of Sec. Secondly, this enzyme does not act on iodothyronines but specifically catalyzes the IRD of TA3 and TA4. This is interesting as the TH receptor of B. floridae is activated by TA3 but not by T3. This suggests that TA3 may be the primordial bioactive TH. Keywords: amphioxus, deiodinase, Iodothyronines, Selenoprotein, Thyroid hormone, Triac Conference: NASCE 2011: The inaugural meeting of the North American Society for Comparative Endocrinology, Ann Arbor, United States, 13 Jul - 16 Jul, 2011. Presentation Type: Invited Symposium Topic: Thyroid Citation: Visser TJ (2011). Regulation of thyroid hormone bioactivity by deiodinases; from invertebrates to humans. Front. Endocrinol. Conference Abstract: NASCE 2011: The inaugural meeting of the North American Society for Comparative Endocrinology. doi: 10.3389/conf.fendo.2011.04.00051 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 08 Jul 2011; Published Online: 09 Aug 2011. * Correspondence: Prof. Theo J Visser, Erasmus University Medical Center, Internal Medicine, Rotterdam, 3015 GE, Netherlands, t.j.visser@erasmusmc.nl Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Theo J Visser Google Theo J Visser Google Scholar Theo J Visser PubMed Theo J Visser Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.