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      The Thyroid Hormone Receptors: Molecular Basis of Thyroid Hormone Resistance

      Hormone Research in Paediatrics

      S. Karger AG

      T3 receptor, Thyroid hormone resistance, T3 action

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          Abstract

          Major progress has been achieved in the mechanism of action of thyroid hormones thanks to the identification of the T<sub>3</sub> receptor as the product of the proto-oncogene c-erbA. Recognition of subsets of receptors with and without T<sub>3</sub>-binding properties and of the interaction of different receptors with each other leads to new insights in cell regulation and development. In thyroid hormone resistance, distinct mutations in the T<sub>3</sub>-binding domain of thyroid hormone receptor (TR)β have been identified in unrelated families. No correlation between the type of mutation and tissue resistance has been established. Mutant TRs bind to thyroid hormone response elements (TREs) on both negative or positive T<sub>3</sub>-controlled genes. Subjects with heterozygous TRβ gene deletion are not affected, supporting the hypothesis that mutant TRs act through a dominant negative effect. In generalized thyroid hormone resistance, mutated TRβ may interfere through competition for TREs and/or formation of inactive dimers. Finally, deficiency in T<sub>3</sub> receptor auxiliary protein or other accessory proteins or competition between mutant and normal TRs for these factors is not excluded.

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          Author and article information

          Journal
          HRE
          10.1159/issn.0018-5051
          Hormone Research in Paediatrics
          S. Karger AG
          978-3-8055-5784-9
          978-3-318-01952-0
          0018-5051
          2571-6603
          1992
          1992
          03 December 2008
          : 38
          : 1-2
          : 57-61
          Affiliations
          Hormone and Metabolism Unit, International Institute of Cellular and Molecular Pathology (ICP), Nuclear Medicine and Clinical Chemistry Departments, University of Louvain Medical School, Brussels, Belgium
          Article
          182487 Horm Res 1992;38:57–61
          10.1159/000182487
          © 1992 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          Page count
          Pages: 5
          Categories
          Hormonal Resistance Syndromes

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