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
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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“In the case of THR, there is no therapy that completely corrects the underlying defect, but treatments with thyroid hormone analogs have been investigated to improve symptoms without excessive activation of the a thyroid hormone receptor, which would worsen cardiac prognosis.91”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [91]
In the citing paper
“In the case of THR, there is no therapy that completely corrects the underlying defect, but treatments with thyroid hormone analogs have been investigated to improve symptoms without excessive activation of the a thyroid hormone receptor, which would worsen cardiac prognosis.91”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [91]
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Metadata
- Authors
- Yao, B., Yang, C., Pan, C., & Li, Y.
- Affiliations
- Xiamen University (CN)
- Corresponding author
- Yang, Chunyan
- Li, Yong
- Venue
- Molecular and Cellular Endocrinology
- Publisher
- Elsevier BV
- Published
- 2022-08
- Volume
- 553
- Pages
- 111679
- ISSN
- 0303-7207 (ISSN-L)
- 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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