Molecular Basis of Nongenomic Actions of Thyroid Hormone

Paul J. Davis, Jack L. Leonard, Hung Yun Lin, Matthew Leinung, Shaker A. Mousa

Research output: Contribution to journalReview article

8 Citations (Scopus)

Abstract

Nongenomic actions of thyroid hormone are initiated by the hormone at receptors in the plasma membrane, in cytoplasm, or in mitochondria and do not require the interaction of nuclear thyroid hormone receptors (TRs) with their primary ligand, 3,5,3'-triiodo-l-thyronine (T3). Receptors involved in nongenomic actions may or may not have structural homologies with TRs. Certain nongenomic actions that originate at the plasma membrane may modify the state and function of intranuclear TRs. Reviewed here are nongenomic effects of the hormone-T3 or, in some cases, l-thyroxine (T4)-that are initiated at (a) truncated TRα isoforms, e.g., p30 TRα1, (b) cytoplasmic proteins, or (c) plasma membrane integrin αvβ3. p30 TRα1 is not transcriptionally competent, binds T3 at the cell surface, and consequently expresses a number of important functions in bone cells. Nongenomic hormonal control of mitochondrial respiration involves a TRα isoform, and another truncated TRα isoform nongenomically regulates the state of cellular actin. Cytoplasmic hormone-binding proteins involved in nongenomic actions of thyroid hormone include ketimine reductase, pyruvate kinase, and TRβ that shuttle among intracellular compartments. Functions of the receptor for T4 on integrin αvβ3 include stimulation of proliferation of cancer and endothelial cells (angiogenesis) and regulation of transcription of cancer cell survival pathway genes. T4 serves as a prohormone for T3 in genomic actions of thyroid hormone, but T4 is a hormone at αvβ3 and more important to cancer cell function than is T3. Thus, characterization of nongenomic actions of the hormone has served to broaden our understanding of the cellular roles of T3 and T4.

Original languageEnglish
Pages (from-to)67-96
JournalVitamins and Hormones
DOIs
Publication statusPublished - 2018

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Keywords

  • Angiogenesis
  • Apoptosis
  • Cancer
  • Cytoskeleton
  • Nanoparticulate tetrac
  • Tetraiodothyroacetic acid
  • Thyroid hormone receptor
  • αv integrin monomer
  • αvβ3 integrin

ASJC Scopus subject areas

  • Physiology
  • Endocrinology

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