Bisphenols and Thyroid Hormone

In recent decades, attention has been directed toward the effects of bisphenol A (BPA) on human health. BPA has estrogenic activity and is regarded as a representative endocrine disruptor. In addition, mounting evidence indicates that BPA can disrupt thyroid hormone and its action. This review examined human epidemiological studies to investigate the association between BPA exposure and thyroid hormone levels, and analyzed in vivo and in vitro experiments to identify the causal relationship and its mechanism of action. BPA is involved in thyroid hormone action not only as a thyroid hormone receptor antagonist, but also through several other mechanisms. Since the use of bisphenols other than BPA has recently increased, we also reviewed the effects of other bisphenols on thyroid hormone action.

Clinical characteristics of thyroid hormone resistance syndrome in two cases with different subtypes / 中华儿科杂志

Objective@#To analyze the clinical characteristics of children with two types of thyroid hormone resistance (RTH) syndrome, and to detect the variants of thyroid hormone receptor alpha(TRα) and TRβ gene in children.@*Method@#Two children with RTH were reported in regard to clinical manifestation, laboratory examination and genetic variants. Some related reports in literature were reviewed.@*Result@#Case 1 was a girl, 10 years old, with thyroid enlargement for several days and without thyrotoxicosis. Laboratory work-up revealed that free thyroxine (FT4) was 65.77 pmol/L (reference 12-22) , free triiodothyronine (FT3) was 15.36 pmol/L (reference 3.1-6.8) and thyroid stimulating hormone (TSH) level was normal. There was a likely pathogenic missense variant detected in TRβ gene and this patient was diagnosed with RTHβ. Case 2 was a boy, 3 years old, with classic features of hypothyroidism(growth retardation, developmental retardation, skeletal dysplasia) but had only borderline-abnormal thyroid hormone levels. Targeted sequencing showed a de novo heterozygous nonsense variant in TRα gene which is a pathogenic variant and this patient been diagnosed with RTHα.@*Conclusion@#Thyroid enlargement is a common clinical manifestation of RTHβ, with laboratory work-up reveals elevated FT4 and FT3 levels but TSH level is normal. The clinical manifestations of RTHα are similar to those of hypothyroidism, but the thyroid hormone levels are almost normal. The gene sequence and the pathogenicity analysis for TRα and TRβ will help to make a definitive diagnosis.

Análise molecular do EXON 10 do gene receptor de TSH em pacientes com tumores da tireóide / Molecular analysis of EXON 10 of TSH receptor gene in patients with thyroid tumors

Introdução: O câncer da tireoide é a quinta neoplasia mais frequente entre as mulheres. A incidência dessa doença vem aumentando substancialmente nos últimos anos. Objetivos: O objetivo do estudo foi determinar a frequência do polimorfismo D727E no gene tshr e associar aos diferentes fenótipos clínicos de tumores de tireoide. Método: 48 pacientes portadores de tumores da tireoide foram operados em hospital de referência de Belém (Pará, Brasil). O grupo-controle foi composto de 131 indivíduos livres de doenças da tireóide. Resultados: Foram encontrados 26 pacientes com tumores malignos e 22 benignos. A frequência alélica do polimorfismo D727E foi de 17,7% em pacientes com tumor de tireoide e 8% no grupo-controle (p<0,03). O polimorfismo D727E mostrou-se em heterozigose em seis pacientes dos 23 com carcinoma papilar e em um com carcinoma folicular. Um paciente com carcinoma folicular e um com carcinoma indiferenciado não apresentaram o polimorfismo. Sete pacientes dos 15 com bócio colóide apresentaram D727E (seis em heterozigose e um em homozigose). Dois dos seis pacientes com adenoma folicular apresentaram o polimorfismo. Discussão: A análise da distribuição da idade de pacientes com câncer mostrou que houve diferença entre os pacientes com diagnóstico de câncer (48,7±14,7 anos) em relação a pacientes com doença benigna (37,8±11,7 anos). A idade de início dos sintomas, que melhor separa os grupos, foi 46 anos. As variáveis gênero feminino, antecedente familiar e idade >41 anos foram associadas à presença do polimorfismo D727E (p = 0,026), o que não foi observado nos pacientes que não apresentavam o polimorfismo. A ocorrência simultânea dos fatores: gênero feminino, antecedente familiar e idade > 46 anos foi relacionada com maior frequência em pacientes com patologia maligna da tireóide (p=0,0047). Conclusões: Estudos adicionais com um maior tamanho amostral são necessários para investigar com mais força estatística a relevância do polimorfismo D727E na gênese do câncer de tireoide e do bócio nodular coloide.

Introduction: Cancer of the thyroid gland is the fifth most common malignancy among women. The disease’s incidence has been increasing over the years. Objectives: The aim of this study, was to determine the frequency of polymorphism D727E tshr gene and its association with different clinical phenotypes of thyroid cancer. Results: 48 patients with thyroid surgical diseases were operated in the city of Belém (Pará, Brazil). The control group was composed by 131 individuals free thyroid diseases. We observed 26 patients with thyroid malignant disease and 22 benign. The allele frequency of polymorphism D727E was 17.7% in patients with thyroid tumor and 8% in the control group (p <0.03). Among malignant thyroid tumors, D727E mutation was found in heterozygosis in 6 of the 23 patients with papillary thyroid carcinoma and in one of two patients with follicular carcinoma. Among the considered benign thyroid tumors: 7 out of 15 patients with nodular goiter colloid showed the mutation (6 heterozygous and 1 homozygous). Two of 6 patients with follicular adenoma showed polymorphism D727E. Discussion: The analysis of the age distribution of patients with thyroid cancer showed that there were differences between patients with cancer diagnosis (48.7 ± 14.7 years), compared to patients with benign disease (37.8 ± 11.7 years). The age of onset of the symptoms that best separates the groups was 46 years. The variables gender (female), family history and age > 41 years were associated with the presence of D727E polymorphism (p = 0.026), which was not observed in patients without this polymorphism. The simultaneous occurrence of gender (female), family history and age > 46 years was associated with increased frequency in patients with malignant thyroid pathology (p = 0.0047). Conclusions: Additional studies with a larger sample size are needed to investigate harder statistical relevance of polymorphism D727E in the genesis of thyroid cancer as well as nodular goiter.

Proliferative effects induced by triiodothyronine in human thyroidal carcinoma cells and their relationship with thyroid receptors / 肿瘤研究与临床

Objective To investigate the proliferation effects induced by triiodothyronine (T3) in thyroid cancer cell lines,including follicular thyroid carcinoma cells (WRO),interstitial thyroid cancer cells (ARO) and papillary thyroid cancer cells (FB-2) and relationship with the thyroid receptor.Methods Different concentrations of thyroid hormone T3 inter acted on the three thyroid cancer cell lines,detected by MTT assay,achieved effective biological dose.To detect proliferation rates in all the cell lines using MTT assay,under the effective biological dose.RT-PCR and Western blot were used to detect the mRNA and protein expression of thyroid receptor.Results Cell proliferation induced depend on different concentrations (10 nmol/L,100 nmol/L and 1 μmol/L) thyroid hormone T3 in thyroid cancer cells FB-2,the proliferation rates were (128.78±0.31) ％,(171.94±0.40) ％,(178.04±0.14) ％,had dose-dependent relationship,which was the most effective physiological dose of 100 nmol/L,cell proliferation was significantly in WRO and ARO under 100 nmol/L[(149.06±0.06) ％,(158.87±0.03) ％],obviously in FB-2 [(167.92±0.08) ％].The expression in mRNA levels of thyroid receptor subtype TRα1 in WRO cells was more,low and no expression in the FB-2 and ARO,did not protein expression,mRNA and protein of subtype TRβ1 expressed in FB-2 and WRO cells,while expressed very little in ARO cells.Conclusion Thyroid hormone T3 can induce thyroid cell proliferation and expression of TRβ1 is relatively important.

Effect of environmental enrichment on thyroid hormone and thyroid hormone receptor in chronic cerebral hypoperfusion rats / 中华神经科杂志

objective To observe the changes of learning and memory,thyroid hormone and thyroid hormone receptor in chronic cerebral hypoperfusion in rats,as well as the effects of enriched environment.MethodsThe rats were randomly divided into 4 groups:sham + standard environment group (sham + SE),2-VO + standard environment group (2-VO + SE),sham + enriched environment group (sham + EE)and 2-VO + enriched environment group(2-VO + EE). Morris water maze,radioimmunoassay,immunohistochemistry and Western blotting methods were used to detect changes in learning and memory in rats,serum thyroid hormone levels and hippocampus thyroid hormone receptors levels.ResultsMorris water maze showed that compared to the control group,the 2-VO + SE rats took more time to find the platform in day 2,4 and 5,the difference was significant (t =2.67,2.67 and 3.18;P ＜ 0.05,P ＜ 0.05 and P ＜ 0.01,respectively) ; and which could be restored by enriched environment in day 4 and 5 ( t =4.08 and 3.55,both P ＜0.01 ).The time spent in the target quadrant in 2-VO + SE rats was significantly shorter than the sham group ( t =3.33,P ＜ 0.05 );and which could be restored by enriched environment ( t =4.46,P ＜ 0.01 ).Radioimmunoassay test showed serum T3 levels had a decreased trends in 2-VO + SE rats compared the control; and which could be restored by enriched environment ( t =3.62,P ＜0.01 ).Immunohistochemistry showed that compared to the sham group,the thyroid hormone receptor α1 in hippocampus CA1 and DG areas was significantly lower in 2-VO + SE rats ( t =3.18 and 3.20,both P ＜0.05 ) ; and which could be restored by enriched environment (t =3.93 and 4.12,both P ＜0.01 ).Western blotting results indicated that compared to the sham group,the hippocampus TRα1 was significantly lower in 2-VO + SE rats ( t =4.35,P ＜0.05 ) ; and which could be restored by enriched environment ( t =6.20,P ＜0.01 ). Conclusion Chronic cerebral hypoperfusion can damage the hippocampus-related learning and memory,and which can be restored by enriched environment; serum T3 and hippocampus TRα1 may be involved in the restorations of enriched environment.

Progress in the study of molecular mechanisms in thyroid hormone insensitive syndrome / 中华内分泌代谢杂志

Thyroid hormone insensitive syndrome is an inherited disease characterized by decreased target tissue responsiveness to thyroid hormone. Most cases are due to thyroid hormone receptor β gene mutation. Two novel types of thyroid hormone insensitive syndrome were recently identified, which are caused by gene mutations of MCT8, a specific thyroid hormone transporter, and SBP2 in the synthesis of deiodinase.