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Molecular Mechanisms of Nuclear Thyroid Hormone Action

  • Chapter
Diseases of the Thyroid

Part of the book series: Contemporary Endocrinology ((COE,volume 2))

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Abstract

The role of thyroid hormone (l-triiodothyronine, T3; L-tetraiodothyronine, T4; TH) in the regulation of diverse cellular activities, including normal growth and development, and general metabolism, is well established (1–4). TH exerts its major effects at the genomic level, although action at nongenomic sites such as the plasma membrane, cytoplasm, mitochondrion, and so on, is also evident (see Chapter 2). Much work in the field, especially over the past decade, has developed a better understanding of the molecular mechanisms involved in TH action and gene transcription (5,6). As illustrated in Fig. 1, circulating free TH enters the cell by either passive diffusion or other yet poorly described mechanisms. In addition, the more biologically active T3 may be generated from T4 in some tissues by iodothyronine 5 ′-deiodinases, and both T3 and T4 may be subject to further intracellular inactivation. TH then enters the nucleus where it binds to the nuclear thyroid hormone receptor (TR) with high affinity and specificity (Kds in the nanomolar range). TR is a ligand-regulated transcription factor that is intimately associated with chromatin, and also associates with additional nuclear proteins to form heterodimers. These, in turn, are bound to target DNAs known as TH-response elements (TREs). The formation of a liganded TR/DNA complex leads to activation of its associated gene, and consequent changes in mRNA and protein. Thus, the central role of TR in nuclear TH action is evident.

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  1. William W. Chin MD
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  2. Paul M. Yen MD
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Editors and Affiliations

  1. Division of Endocrinology and Metabolism, University of Massachusetts Medical Center, Worcester, Massachusetts, USA

    Lewis E. Braverman MD

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Chin, W.W., Yen, P.M. (1997). Molecular Mechanisms of Nuclear Thyroid Hormone Action. In: Braverman, L.E. (eds) Diseases of the Thyroid. Contemporary Endocrinology, vol 2. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-4757-2594-0_1

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  • DOI: https://doi.org/10.1007/978-1-4757-2594-0_1

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