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Cited by 26Thyroid Disorders and TreatmentsEstrogen and related hormone effectsGrowth Hormone and Insulin-like Growth Factors

The DOI matches its Crossref record; 252 of the 257 references it cites were found in a registry or an index.

Thyroid hormone resistance: Mechanisms and therapeutic development

Yao, Benqiang, Yang, Chunyan, Pan, Chengxi, Li, Yong·2022·Molecular and Cellular Endocrinology
DOI 10.1016/j.mce.2022.111679
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Abstract

As an essential primary hormone, thyroid hormone (TH) is indispensable for human growth, development and metabolism. Impairment of TH function in several aspects, including TH synthesis, activation, transportation and receptor-dependent transactivation, can eventually lead to thyroid hormone resistance syndrome (RTH). RTH is a rare syndrome that manifests as a reduced target cell response to TH signaling. The majority of RTH cases are related to thyroid hormone receptor β (TRβ) mutations, and only a few RTH cases are associated with thyroid hormone receptor α (TRα) mutations or other causes. Patients with RTH suffer from goiter, mental retardation, short stature and bradycardia or tachycardia. To date, approximately 170 mutated TRβ variants and more than 20 mutated TRα variants at the amino acid level have been reported in RTH patients. In addition to these mutated proteins, some TR isoforms can also reduce TH function by competing with primary TRs for TRE and RXR binding. Fortunately, different treatments for RTH have been explored with structure-activity relationship (SAR) studies and drug design, and among these treatments. With thyromimetic potency but biochemical properties that differ from those of primary TH (T3 and T4), these TH analogs can bypass specific defective transporters or reactive mutant TRs. However, these compounds must be carefully applied to avoid over activating TRα, which is associated with more severe heart impairment. The structural mechanisms of mutation-induced RTH in the TR ligand-binding domain are summarized in this review. Furthermore, strategies to overcome this resistance for therapeutic development are also discussed.

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Research works printed but not linked: 12

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Metadata

Authors
Yao, B., Yang, C., Pan, C., & Li, Y.
Affiliations
Xiamen University (CN)
Corresponding author
  • Yang, Chunyan
  • Li, Yong
ORCID
Venue
Molecular and Cellular Endocrinology
Publisher
Elsevier BV
Published
2022-08
Volume
553
Pages
111679
ISSN
0303-7207 (ISSN-L)
DOI
10.1016/j.mce.2022.111679
OpenAlex
W4283168004
Semantic Scholar
1b55c5412d9ac36b45f4511fb0cfbea61939b35e
Cited by
26
References
257
Citations by year
2026: 5 · 2025: 6 · 2024: 6 · 2023: 9
FWCI
3.89
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Molecular and Cellular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
thyroid hormone resistance, thyroid hormone receptor beta, thyroid hormone receptor alpha, structure-activity relationship, drug design, goiter, bradycardia, short stature, intellectual disability
MeSH terms
Humans, Mutation, Receptors, Thyroid Hormone, Thyroid Hormones, Triiodothyronine, Thyroid Hormone Resistance Syndrome, Thyroid Hormone Receptors alpha, Thyroid Hormone Receptors beta

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