Thyroid hormone resistance: Mechanisms and therapeutic development

Yao, Benqiang; Yang, Chunyan; Pan, Chengxi; Li, Yong

doi:10.1016/j.mce.2022.111679

Cited by 11 publications

(11 citation statements)

References 229 publications

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“…Our study consisted of examining the probability of PFAS binding to thyroid α and β sites, respectively: 3ILZ (structure of TRα bound to selective thyromimetic GC-1 in P212121 space group [ 61 ] and 3IMY (structure of TRβ bound to selective thyromimetic GC-1 [ 62 ]. The binding of a ligand (GC-1) to sites selected for PFAS docking induces positive effects, such as lowering serum LDL cholesterol and triglycerides, so PFAS binding may interfere with this process [ 63 ].…”

Section: Resultsmentioning

confidence: 99%

How the Structure of Per- and Polyfluoroalkyl Substances (PFAS) Influences Their Binding Potency to the Peroxisome Proliferator-Activated and Thyroid Hormone Receptors—An In Silico Screening Study

Kowalska¹,

Sosnowska²,

Buławska³

et al. 2023

Molecules

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In this study, we investigated PFAS (per- and polyfluoroalkyl substances) binding potencies to nuclear hormone receptors (NHRs): peroxisome proliferator-activated receptors (PPARs) α, β, and γ and thyroid hormone receptors (TRs) α and β. We have simulated the docking scores of 43 perfluoroalkyl compounds and based on these data developed QSAR (Quantitative Structure-Activity Relationship) models for predicting the binding probability to five receptors. In the next step, we implemented the developed QSAR models for the screening approach of a large group of compounds (4464) from the NORMAN Database. The in silico analyses indicated that the probability of PFAS binding to the receptors depends on the chain length, the number of fluorine atoms, and the number of branches in the molecule. According to the findings, the considered PFAS group bind to the PPARα, β, and γ only with low or moderate probability, while in the case of TR α and β it is similar except that those chemicals with longer chains show a moderately high probability of binding.

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Section: Resultsmentioning

confidence: 99%

How the Structure of Per- and Polyfluoroalkyl Substances (PFAS) Influences Their Binding Potency to the Peroxisome Proliferator-Activated and Thyroid Hormone Receptors—An In Silico Screening Study

Kowalska¹,

Sosnowska²,

Buławska³

et al. 2023

Molecules

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“…5 In addition, defects of TH cell membrane transport (such as MCT8 defect), 15 TH metabolism (such as selenocysteine insertion sequence binding protein 2 defect) 16 are also causes of rare RTH. 4 In 2019, Laclaustra et al put forward the hypothesis that a mild acquired resistance to THs was widespread among the general population, not a rare inherited defect. 8 THs had effects on energy homeostasis, glucose metabolism, lipid, and BP.…”

Section: Discussionmentioning

confidence: 99%

“…The majority of RTH cases are caused by mutations of TH receptor β, whereas a few RTH cases are caused by mutations of TH receptor α 5 . In addition, defects of TH cell membrane transport (such as MCT8 defect), 15 TH metabolism (such as selenocysteine insertion sequence binding protein 2 defect) 16 are also causes of rare RTH 4 . In 2019, Laclaustra et al put forward the hypothesis that a mild acquired resistance to THs was widespread among the general population, not a rare inherited defect 8 …”

Section: Discussionmentioning

confidence: 99%

“…1 In terms of the relationship between thyroid hormones (THs) and MetS, it was found that hyperthyroidism and hypothyroidism, both overt and subclinical, might be associated with the risk of MetS. 3,4 However, the relationship between the normal range of THs (serum-free thyroxine [FT4], free triiodothyronine [FT3]) and MetS is inconsistent. [5][6][7][8] Recently, it was reported that co-occurrence of high thyrotropin (TSH) and high THs, which represented a kind of mild acquired resistance to thyroid hormones (RTH), was widespread among the general population.…”

Section: Introductionmentioning

confidence: 99%

“…In terms of the relationship between thyroid hormones (THs) and MetS, it was found that hyperthyroidism and hypothyroidism, both overt and subclinical, might be associated with the risk of MetS 3,4 . However, the relationship between the normal range of THs (serum‐free thyroxine [FT4], free triiodothyronine [FT3]) and MetS is inconsistent 5–8 .…”

Section: Introductionmentioning

confidence: 99%

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Sensitivity to thyroid hormone and risk of components of metabolic syndrome in a Chinese euthyroid population

Cai

Li³

et al. 2023

Journal of Diabetes

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IntroductionTo evaluate the association of sensitivity to thyroid hormone with metabolic syndrome (MetS) and its components in a Chinese euthyroid population.MethodsA total of 3573 participants from Pinggu Metabolic Disease Study were analyzed. Serum‐free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), total adipose tissue (TAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) area of abdominal, and lumbar skeletal muscle area (SMA) were measured. Central thyroid hormone resistance was calculated by the Thyroid Feedback Quantile‐based Index (TFQI) and Chinese‐referenced Parametric TFQI (PTFQI), Thyrotroph T4 Resistance Index (TT4RI) and TSH Index (TSHI). Peripheral thyroid hormone resistance was assessed by FT3/FT4 ratio.ResultsHigher values of TSHI (odds ratio [OR] = 1.167, 95% confidence interval [CI]: 1.079–1.262, p < .001), TT4RI (OR = 1.115, 95% CI: 1.031–1.206, p = .006), TFQI (OR = 1.196, 95% CI: 1.106–1.294, p < .001), PTFQI (OR = 1.194, 95% CI: 1.104–1.292, p < .001), and lower values of FT3/FT4 ratio (OR = 0.914, 95% CI: 0.845–0.990, p = .026) were associated with MetS. Increased levels of TFQI and PTFQI were associated with abdominal obesity, hypertriglyceridemia, and hypertension. Increased levels of TSHI and TT4RI were associated with hypertriglyceridemia, abdominal obesity, low high‐density lipoprotein cholesterol. Reduced levels of FT3/FT4 ratio were associated with hyperglycemia, hypertension, and hypertriglyceridemia. The levels of TSHI, TFQI, and PTFQI were negatively related to SMA and positively related to VAT, SAT, and TAT (all p < .05).ConclusionsReduced thyroid hormone sensitivity was associated with MetS and its components. Impaired thyroid hormone sensitivity might affect the distribution of adipose tissue and muscle.

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Effective TRIAC treatment of a THRβ-mutated patient with thyroid hormone resistance

Carbone,

Verrienti,

Cito

et al. 2024

Endocrine

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Thyroid hormone resistance: Mechanisms and therapeutic development

Cited by 11 publications

References 229 publications

How the Structure of Per- and Polyfluoroalkyl Substances (PFAS) Influences Their Binding Potency to the Peroxisome Proliferator-Activated and Thyroid Hormone Receptors—An In Silico Screening Study

How the Structure of Per- and Polyfluoroalkyl Substances (PFAS) Influences Their Binding Potency to the Peroxisome Proliferator-Activated and Thyroid Hormone Receptors—An In Silico Screening Study

Sensitivity to thyroid hormone and risk of components of metabolic syndrome in a Chinese euthyroid population

Effective TRIAC treatment of a THRβ-mutated patient with thyroid hormone resistance

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