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Cited by 1,244Thyroid Disorders and TreatmentsEstrogen and related hormone effectsThyroid Cancer Diagnosis and Treatment

Mechanisms of thyroid hormone action

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Brent, Gregory A.·2012·Journal of Clinical Investigation
DOI 10.1172/jci60047PMC PMC3433956
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Abstract

Our understanding of thyroid hormone action has been substantially altered by recent clinical observations of thyroid signaling defects in syndromes of hormone resistance and in a broad range of conditions, including profound mental retardation, obesity, metabolic disorders, and a number of cancers. The mechanism of thyroid hormone action has been informed by these clinical observations as well as by animal models and has influenced the way we view the role of local ligand availability; tissue and cell-specific thyroid hormone transporters, corepressors, and coactivators; thyroid hormone receptor (TR) isoform-specific action; and cross-talk in metabolic regulation and neural development. In some cases, our new understanding has already been translated into therapeutic strategies, especially for treating hyperlipidemia and obesity, and other drugs are in development to treat cardiac disease and cancer and to improve cognitive function.

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  • Thyroid hormone action affects a wide range of biological pathways, and virtually all organ systems have a measurable response to the administration of replacement or supraphysiologic doses of LT4.

    “Thyroid hormone action affects a wide range of biological pathways, and virtually all organ systems have a measurable response to the administration of replacement or supraphysiologic doses of LT4 (8,9).”

    From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [9]

    The Introduction and Summary say thyroid hormone regulates a wide range of genes and interacts with many signaling pathways. Our copy does not establish that virtually all organ systems show a measurable response to replacement or supraphysiologic LT4 doses; the treatment passages describe more specific effects. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Thyroid hormone action is an important determinant of development and growth, and in adults plays a critical role in the regulation of the function and metabolism of virtually every organ system (8,9).

    “Thyroid hormone action is an important determinant of development and growth, and in adults plays a critical role in the regulation of the function and metabolism of virtually every organ system (8,9).”

    From Guidelines for the Treatment of Hypothyroidism: Prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement (2014) · cites this paper as [9]

  • The findings are broadly consistent with a role for thyroid hormone in balancing proliferation and differentiation.

    “Our findings are broadly consistent with a role for TH in balancing proliferation and differentiation (Brent, 2012)”

    From Thyroid hormone regulates distinct paths to maturation in pigment cell lineages (2019) · cites this paper as Brent, 2012

  • T3 acts by interacting with nuclear TH receptors, changing the rate at which genes are transcribed.

    “The T3 acts by interacting with nuclear TH receptors (TRs), changing the rate at which genes are transcribed.”

    From Liothyronine and Desiccated Thyroid Extract in the Treatment of Hypothyroidism (2020) · cites this paper as [54]

  • TH has insulin-antagonistic effects in the liver and synergistic effects with insulin in peripheral tissues.

    “TH has insulin-antagonistic effects in the liver, whereas it acts synergically with insulin in the peripheral tissues.”

    From Thyroid dysfunction and diabetes mellitus: two closely associated disorders (2019) · cites this paper as [130]

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Authors
Brent, G. A.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Brent, Gregory A.
ORCID
Brent, Gregory A.
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
2012-09-04
Volume
122
Issue
9
Pages
3035-3043
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci60047
PMC
PMC3433956
OpenAlex
W2022349101
Cited by
1,244
References
138
Citations by year
2026: 93 · 2025: 146 · 2024: 139 · 2023: 110 · 2022: 118 · 2021: 117 · 2020: 83 · 2019: 99 · 2018: 72 · 2017: 69 · 2016: 65 · 2015: 39 · 2014: 57 · 2013: 25 · 2012: 2
FWCI
5.46
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • U.S. Department of Veterans Affairs
  • National Institutes of Health
  • VA Greater Los Angeles Healthcare System
  • National Cancer Institute (R01 CA-89364, R01CA089364)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords
thyroid hormone action, thyroid hormone resistance, thyroid hormone transporters, corepressors, transcriptional coactivator, metabolic regulation, neural development, hyperlipidemia, obesity, cognitive function, heart disease, cancer therapy
MeSH terms
Adipose Tissue, Animals, Cell Membrane, Gene Expression Regulation, Humans, Mutation, Neoplasms, Receptors, Thyroid Hormone, Thyroid Hormones, Signal Transduction, Thyroid Hormone Resistance Syndrome, Receptor Cross-Talk, Organogenesis

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