Fructose consumption induces molecular adaptations involving thyroid function and thyroid-related genes in brown adipose tissue in rats

The increasing incidence of metabolic diseases is in part due to the high fructose consumption, a carbohydrate vastly used in industry, with a potent lipogenic capacity. Thyroid hormones (TH) are essential for metabolism regulation and are associated with changes in body weight, energy expenditure, insulin sensitivity, and dyslipidemia. This study aimed to investigate the influence of fructose intake on thyroid function and thyroid-related genes. Male Wistar rats were divided into Control (CT, n=8) and Fructose (FT - 10% in drinking water, n=8) groups for three weeks. The FT group showed higher glycemia and serum triacylglycerol, indicating metabolic disturbances, and increased thyroid mass, accompanied by higher expression of Srebf1c and Lpl, suggesting increased lipid synthesis. The FT group also presented higher expression of Tpo and Dio1 in the thyroid, suggesting activation of the thyroid gland, but with no alterations in serum TH concentrations. Brown adipose tissue (BAT) of the FT group exhibited higher expression of Dio2, Thra, and Thrb, indicating increased T3 intra-tissue bioavailability and signaling. These responses were accompanied by increased BAT mass and higher expression of Adrb3, Pparg, Srebf1c, Fasn, Ppara, and Ucp1, suggesting increased BAT adrenergic sensitivity, lipid synthesis, oxidation, and thermogenesis. Therefore, short-term fructose consumption induced thyroid molecular alterations and increased BAT expression of thyroid hormone-related signaling genes that potentially contributed to higher BAT activity.

Mus musculus: biomodelo de expresión de Desyodinasa (DIO3) y Transtiretina (TTR) en el desarrollo placentario / Mus musculus: an experimental model for Deiodinase (DIO3) and Transthyretin (TTR) expression during placental development / Mus musculus: Biomodelo de expressão de Deiodinase (DIO3) e Transtiretina (TTR) no desenvolvimento da placenta

RESUMEN Introducción: El correcto funcionamiento del eje hipotálamo-hipófisis-tiroides es indispensable para el crecimiento y desarrollo embrionario-fetal, al intervenir en la diferenciación de los tejidos, el desarrollo cerebral y somático, la maduración ósea y la regulación del metabolismo. El paso de las hormonas tiroideas maternas al feto a través de la placenta depende de transportadores transmembrana, enzimas desyodinasas (DIO2 y DIO3) y proteínas transportadoras (TTR). Objetivo: Identificar las zonas de expresión de DIO3 y TTR en la placenta de ratón Mus musculus E10.5, E12.5, E14.5. Métodos: La estructura placentaria y expresión de DIO3 y TTR fueron evaluadas con técnicas histoquímicas e inmunofluorescencia. Resultados: Desde E10.5 se encontraron las tres zonas placentarias, laberinto, zona de unión y decidua. En E12.5 se observó la conformación placentaria definitiva. DIO3 y TTR fueron detectadas en los tres estadios, con predominio en la zona del laberinto. Conclusión: DIO3 y TTR se expresan a lo largo del establecimiento y maduración de la placenta de ratón. El biomodelo murino es una herramienta útil para el estudio del transporte placentario de hormonas tiroideas desde la circulación materna a la fetal.

ABSTRACT Introduction: Correct functioning of hypothalamic-pituitary-thyroid axis is essential for embryonic-fetal growth and development, as it is involved in tissue differentiation, brain and somatic development, bone maturation and metabolic regulation. Maternal thyroid hormones passage to the fetus through the placenta depends on transmembrane transporters, deiodinase enzymes (DIO2 and DIO3) and carrier proteins (TTR). Objective: Identify DIO3 and TTR expression within placental layers of Mus musculus E10.5, E12.5 and E14.5. Methods: Placental structure, DIO3 and TTR expression were evaluated using histochemistry and immunofluorescence techniques. Results: We found that the three placental layers, labyrinth zone, junctional zone, and decidua were present since E10.5. At E12.5 placental final conformation was observed. DIO3 and TTR were detected in the three stages with a predominance in the labyrinth. Conclusion: DIO3 and TTR are expressed throughout the establishment and maturation of mouse placenta. Mice are a useful tool for studying how thyroid hormones are transported from maternal t° fetal circulation at the placenta.

RESUMO Introdução: O correto funcionamento do eixo hipotálamo-hipófise-tireoide é essencial para o crescimento e desenvolvimento embrionário-fetal, pois intervém na diferenciação dos tecidos, desenvolvimento cerebral e somático, maturação óssea e regulaçãodo metabolismo. A passagem dos hormônios tireoidianos maternos para o feto através da placenta depende de transportadores transmembranas, enzimas deiodinase (DIO2 e DIO3) e proteínas transportadoras (TTR). Objetivo: Identificar as zonas de expressão de DIO3 e TTR na placenta de rato Mus musculus E10.5, E12.5, E14.5. Métodos: A estrutura placentária e a expressão de DIO3 e TTR foram avaliadas com técnicas histoquímicas e imunofluorescência. Resultados: De E10.5 as três zonas placentárias, labirinto, zona de união e decídua foram encontradas. Em E12.5 a conformação definitiva da placenta foi observada. O DIO3 e o TTR foram detectados nas três fases, com predomínio na área do labirinto. Conclusão: DIO3 e TTR são expressos ao longo do estabelecimento e maturação da placenta de rato O biomodelo murino é uma ferramenta útil para o estudo do transporte placentário dos hormônios tireoidianos da circulação materna para a fetal.

Effect of Chronic Iodine Excess on Type Ⅱ Deiodinase in Hypothalamus and Serum Thyrotropin Releasing Hormone Level in Rats / 中国医科大学学报

Objective To investigate the effect of chronic iodine excess on hypothalamic type Ⅱ deiodinase (D2) and serum thyrotropin releasing hormone (TRH) levels in rats. Methods One hundred and eighty four-week-old Wistar rats were randomly divided into control group (NI) and 3-fold, 6-fold, 10-fold, and 50-fold high iodine (HI) groups. Double distilled water and iodine solutions at concentrations of 277, 692, 1 245, and 6 788 μg/L were administered for 4, 8, 12, and 24 weeks, respectively. Brain tissue was taken after sacrifice, serum TRH levels were detected by ELISA, and hypothalamic D2 levels were detected by immunohistochemistry. Results Serum TRH levels in the 10-fold and 50-fold HI groups at 4 weeks, 6-fold and 50-fold HI groups at 8 weeks, 6-fold HI group at 12 weeks, and the 3-fold and 50-fold HI groups at 24 weeks were significantly lower than those in the control group (P ＜ 0.05). The results of immunohistochemistry revealed that the expression of hypothalamic D2 at each time-point was increased in the HI groups in comparison with the control group. Conclusion Chronic iodine excess can boost the expression of hypothalamic D2 and lessen the serum TRH level in rats.

Propranolol inhibits myocardial infarction-induced brown adipose tissue D2 activation and maintains a low thyroid hormone state in rats

Considering the recognized role of thyroid hormones on the cardiovascular system during health and disease, we hypothesized that type 2 deiodinase (D2) activity, the main activation pathway of thyroxine (T4)-to-triiodothyronine (T3), could be an important site to modulate thyroid hormone status, which would then constitute a possible target for β-adrenergic blocking agents in a myocardial infarction (MI) model induced by left coronary occlusion in rats. Despite a sustained and dramatic fall in serum T4 concentrations (60-70%), the serum T3 concentration fell only transiently in the first week post-infarction (53%) and returned to control levels at 8 and 12 weeks after surgery compared to the Sham group (P<0.05). Brown adipose tissue (BAT) D2 activity (fmol T4·min-1·mg ptn-1) was significantly increased by approximately 77% in the 8th week and approximately 100% in the 12th week in the MI group compared to that of the Sham group (P<0.05). Beta-blocker treatment (0.5 g/L propranolol given in the drinking water) maintained a low T3 state in MI animals, dampening both BAT D2 activity (44% reduction) and serum T3 (66% reduction in serum T3) compared to that of the non-treated MI group 12 weeks after surgery (P<0.05). Propranolol improved cardiac function (assessed by echocardiogram) in the MI group compared to the non-treated MI group by 40 and 57%, 1 and 12 weeks after treatment, respectively (P<0.05). Our data suggested that the beta-adrenergic pathway may contribute to BAT D2 hyperactivity and T3 normalization after MI in rats. Propranolol treatment maintained low T3 state and improved cardiac function additionally.

Effect of acetaminophen on thyroxine relative genes of zebrafish embryos / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effects of N-acetyl-p-aminophenol (APAP) on zebrafish pigments and thyroxine related genes. METHODS Well-developed zebrafish embryos were exposed to APAP 0, 2, 4 and 8 mmohL-1 from 4 h post fertilization (hpf) and observed at 24, 48, 72 and 96 hpf, respectively, each with 3 replicates. Image J was used to detect the change of pericardial edema of zebrafish. The conentrations of triiodothyronine and tetraiodothyronine were determined by ELISA. mRNA of thyroxine relative genes TPO, Trh, Dio2, Dio3, Thru and Thrf} was detected by fluorescent quantitative PCR. RESULTS At 72 hpf, compared with control group, the hatching rate and pigmentation accumulation decreased in APAP 8 mmol • L-1 group (FcO.OI), but the pericardial area was increased (P<0.01). The conentrations of tetraiodothyronine and triiodothyronine were decreased in APAP 8 mmol • L-1 group (P<0.05). Quantitative PCR results showed that APAP down-regulated mRNA levels of TPO, Trh and Thrfi in APAP 8 mmol-L-1 exposure group (P<0.05). There was no statistically significant difference in the expression of other genes. CONCLUSION The decrease in pigmentation and hatching rate caused by APAP may be related to the decreased expressions of thyroid hormone-related genes.

The establishment of zebrafish Dio3b gene knockout model / 中华内分泌代谢杂志

Objective To set up the model of deiodinase ( Dio) 3b-/- zebrafish and to observe the effect of which on embryo development. Methods The zebrafish model of Dio3b-/- was set up by CRISPR-Cas9 gene editing technology, PCR and sequencing was used to confirm the efficiency of deletion. The heart rate of embryos at 48 hours post fertilization was counted. The locomotor activity of 5-7 days post fertilization larve was detected using behavior tracking system. Results The model of Dio3b knockout zebrafish was set up successfully. The heart rate of embryos Dio3b-/- increased ( P＜0. 001) and the locomotor activity of 5-7 days post fertilization larves lacking Dio3b gene increased (P＜0.05) significantly compared with that of wild type control respectively. Conclusion The deletion of zebrafish Dio3b gene results in the phenotype of hyperthyroidism and the model of Dio3b-/- is proper for studying the effect of partial excess thyroid hormone on embryo development.

Metastatic follicular thyroid carcinoma as a cause of low serum thyroxine with a normal thyroid stimulating hormone level / Journal of the ASEAN Federation of Endocrine Societies

@#Thyroid function is usually normal in differentiated thyroid carcinoma. We describe a case of a female patient who had metastatic follicular thyroid carcinoma (FTC) to the spine and lungs, who was clinically euthyroid but had very low free tetraiodothyronine (fT4) and normal thyroid stimulating hormone (TSH). Free triiodothyronine (fT3) and total T3 (TT3) were normal. Levothyroxine treatment increased fT4 marginally but caused a two- to three-fold rise in fT3 and TT3 along with suppressed TSH. This is likely due to hyperconversion of T4 to T3 from elevation in D2 deiodinase activity in the tumor. This phenomenon has been reported to occur in about 20% of metastatic FTC.

Metastatic Follicular Thyroid Carcinoma as a cause of low serum thyroxine with a Normal Thyroid stimulating hormone level / Journal of the ASEAN Federation of Endocrine Societies

@#Thyroid function is usually normal in differentiated thyroid carcinoma. We describe a case of a female patient who had metastatic follicular thyroid carcinoma (FTC) to the spine and lungs, who was clinically euthyroid but had very low free tetraiodothyronine (fT4) and normal thyroid stimulating hormone (TSH). Free triiodothyronine (fT3) and total T3 (TT3) were normal. Levothyroxine treatment increased fT4 marginally but caused a two- to three-fold rise in fT3 and TT3 along with suppressed TSH. This is likely due to hyperconversion of T4 to T3 from elevation in D2 deiodinase activity in the tumor. This phenomenon has been reported to occur in about 20% of metastatic FTC.

Synergic actions of polyphenols and cyanogens of peanut seed coat (Arachis hypogaea) on cytological, biochemical and functional changes in thyroid.

In animals, long-term feeding with peanut (Arachis hypogaea) seed coats causes hypertrophy and hyperplasia of the thyroid gland. However, to date there have been no detailed studies. Here, we explored the thyroidal effects of dietary peanut seed coats (PSC) in rats. The PSC has high levels of pro-goitrogenic substances including phenolic and other cyanogenic constituents. The PSC was mixed with a standard diet and fed to rats for 30 and 60 days, respectively. Animals fed with the PSC-supplemented diet showed a significant increase in urinary excretion of thiocyanate and iodine, thyroid enlargement, and hypertrophy and/or hyperplasia of thyroid follicles. In addition, there was inhibition of thyroid peroxidase (TPO) activity, 5’-deiodinase-I (DIO1) activity, and (Na+-K+)-ATPase activity in the experimental groups of rats as compared to controls. Furthermore, the PSC fed animals exhibited decreased serum circulating total T4 and T3 levels, severe in the group treated for longer duration. These data indicate that PSC could be a novel disruptor of thyroid function, due to synergistic actions of phenolic as well as cyanogenic constituents.

Variação transcardíaca da concentração dos hormônios tireoidianos induzida por hipóxia miocárdica em pacientes submetidos à circulação extracorpórea / Transcardiac thyroid hormone variation induced by myocardial hypoxia in patients undergoing cardiopulmonary bypass

As doenças cardíacas são a principal causa de morte em todo o mundo. Os hormônios tireoidianos desempenham um papel chave no metabolismo miocárdico e na fisiologia do sistema cardiovascular. A doença cardíaca aguda ou crônica promove uma queda sistêmica da concentração dos hormônios tireoidianos que se associa a um prognóstico pior da doença e aumento da sua mortalidade. Essa redução dos hormônios tireoidianos pode ocorrer na presença de função normal da tireóide, entidade clínica conhecida por síndrome da doença não-tireoidiana ou síndrome do enfermo eutireoideo (SEE). A participação do músculo cardíaco na patogênese da SEE é desconhecida. O entendimento do papel do músculo cardíaco na SEE é essencial para o tratamento das doenças cardíacas. Este estudo se propõe a avaliar a variação dos hormônios tireoidianos promovida pelo metabolismo cardíaco nos pacientes submetidos a cirurgias cardíacas com diferentes graus de isquemia miocárdica aguda, bem como estudar os principais mecanismos envolvidos nessa variação. Para avaliar a variação sistêmica de hormônios tireoideanos induzida pela cirurgia cardíaca com e sem circulação extracorpórea (CEC), 35 pacientes com estenose aórtica grave e doença coronariana submetidos à cirurgia com CEC e 12 pacientes submetidos à cirurgia de revascularização miocárdica sem CEC tiveram as concentrações sistêmicas dos hormônios tireoidianos dosadas no início do procedimento cirúrgico, imediatamente antes do clampeamento da aorta, 3 minutos após o desclampeamento da aorta, 6 e 24h após o procedimento. Além disso, a avaliação da participação isolada do coração foi feita pela dosagem dos hormônios tireoidianos na raiz da aorta e no seio coronário antes e após a isquemia miocárdica aguda induzida pelo clampeamento da aorta. Foram ainda quantificadas, em amostras do tecido miocárdico colhidas após a CEC, a expressão do gene das desiodades, enzimas responsáveis pela conversão dos hormônios tireoidianos nos tecidos...

Heart diseases are the main cause of death over the world and thyroid hormones are key elements in myocardial metabolism and cardiovascular physiology. In heart disease patients, low thyroid hormone levels lead to a worse prognosis and increase in the mortality, even with regular thyroid function, in a condition known as Euthyroid Sick Syndrome (ESS). There is no evidence that myocardial tissue is involved in ESS pathophysiology. The better understanding of heart role might be important to optimal treatment of heart disease. The current study aims to evaluate thyroid hormones variation induced by myocardial metabolism in patients submitted to several acute myocardial ischemic intensities and study the main mechanisms associated to this condition. To reach this objective, 35 stable severe aortic stenosis coronary artery disease submitted to in-pump cardiac surgery and 12 patients submitted to off-pump myocardial revascularization surgery were analyzed at the procedure beginning, before aortic clamping, 3 minutes after aortic cross-clamp release, six and 24h after procedure by measuring thyroid hormones concentration in systemic circulation. Therefore, cardiac metabolism was evaluated alone by the thyroid hormones concentration measurement in aortic root and coronary sinus just before and after myocardial ischemia induced by aortic clamping, as well the gene expression of thyroid hormones metabolism related enzyme in myocardial tissue samples. There was a significant 37.6% reduction in T3 systemic concentration, a 261.6% elevation in rT3 and no variation in free T4 systemic values during the observation time in three groups. However, there were no statistically differences among the groups. Central analysis showed a 4.6% significant reduction in T3 and 6.9% increase in rT3 in coronary sinus, compared to aortic root, in aortic stenosis group before cardiopulmonary bypass. The same behavior was not observed in coronary artery disease before aortic...

Goitrogenic and Antithyroid Potential of Green Tea Of Indian Origin.

Polyphenolic flavonoids, specially catechins are major constituents of tea. Antithyroidal and goitrogenic effect of flavonoids have been reported however such effects of green tea on thyroid physiology has not been explored earlier. Green tea is derived from the tea leaves of Camellia sinensis and widely consumed globally. The green tea extracts(GTE) at different concentrations (1.25g% a” 5 cups of tea/ day; 2.5g% a” 10 cups of tea/ day and 5.0g% a” 20 cups of tea/ day) were orally fed to male rats for 30 days. Similarly, pure catechin was administered orally to male albino rats for 30 days at doses of 25, 50 and 100 mg/kg body weight that are equivalent to above doses of green tea extract in terms of its total catechin content and the morphological and functional changes of the thyroid have been investigated. The overall results reveal that oral administration of green tea extract at 2.5g% and 5.0g% concentrations for 30 days changed the morphology and histology resembling hypertrophy of thyroid follicles with differential colloid sizes as found in hypothyroid due to environment influences associated with significant inhibited activities of thyroid peroxidase(TPO) and 5’ monodeiodinase (5’ DI1) with elevated Na+,K+ ATPase and concomitant decrease in serum thyroxine (T4), triiodothyronine (T3) and increase in serum thyrotropin (TSH) levels developing a state of absolute biochemical hypothyroidism. All these suggest that catechin present in green tea has the antithyroidal as well as goitrogenic potential and its regular consumption at relatively high doses pose a threat to the functioning of thyroid.

Changes of iodothyronine deiodinase type 1 and type 3 mRNA level and activity in liver of mice with endotoxemia / 中华实用儿科临床杂志

Objective To explore the effect of endotoxemia on triiodothyronine (T3) and thyroxine (T4),and the level and activity of iodothyronine deiodinase type 1 and type 3 mRNA.Methods Sixteen mice were randomly divided into control group and lipopolysaccharide (LPS) group,with 8 mice in each group.The mouse model of endotoxemia was replicated in the LPS group.In the both groups,blood samples from femoral week were collected to assay T3 and T4 levels,and the livers were sampled to inspect D1 and D3 mRNA levels and activities.Serum T3 and T4 levels were assayed with radioimmunoassay,D1 and D3 mRNA levels in liver were detected with real-time polymerase chain reaction,the activity of D1 and D3 in liver were measured by using ion-exchange chromatography combined with immunoassay.The data were statistically analyzed by SPSS 13.0 software.Results Statistical differences of T3,D1 and D3 mRNA levels and activities between the 2 groups were found (all P ＜0.01),while,there was no statistic difference in the statuses of T4 (P ＞ 0.05).Conclusions It is possible that euthyroid sick syndromes happens in endotoxemia episodes,and the changes of D1 and D3 mRNA levels and activities are the possible influencing factors.

Expression of iodothyronine deiodinases on human placenta in pregnant women with different thyroid disease / 中国综合临床

Objective To investigate the expression of type Ⅱ and type Ⅲ iodothyronine deiodinases (D2 and D3 ) of human placenta on pregnant women with different thyroid diseases and different autoimmunity.Methods Pregnant women with different thyroid diseases and autoimmunity were selected into the experiment group,and pregnant women who had no individual or family history of thyroid diseases with normal thyroid function and negative thyroid peroxidase antibody (TPOAb) were selected into the control group.Expression level of iodothyronine deiodinase( D2 and D3 )on placenta was measured by RT-PCR.Results D2 and D3 were both expressed on human placenta.D2 showed significantly higher expression level in hypothyroidism uncontrolled group than that in control group ( 0.916 ± 0.035 vs 0.833 ± 0.029,P ＜ 0.05 ),however,D3 showed a lower expression(0.766 ±0.038 vs 0.848 ±0.052),on placenta and the difference was not significant(P ＞ 0.05 ).In those who had history of hyperthyroidism or hypothyroidism but whose thyroid function become normal by effective treatment,D2 and D3 expression exhibited no difference from that of the control(P ＞ 0.05).In those pregnant women with normal thyroid function and TPOAb-positive,D2 and D3 expression was (0.842 ± 0.032 ) and ( 0.837 ± 0.053 ) respectively and there was also no difference from that of the control( P ＞ 0.05 ).Conclusion D2 and D3 were simultaneously expressed on human placenta.In those pregnant women with hypothyroidism,the level of D2 expression is high and the level of D3 expression is low.Those changes might be important and helpful for the stabilization of thyroid hormone transportation between mother and fetus.

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.

Abuso de esteróides anabolizantes e seu impacto sobre a função tireóidea: [revisão] / Abuse of anabolic steroids and its impact on thyroid function: [review]

A utilização de esteróides anabolizantes por indivíduos que desejam aumentar sua performance física, ou simplesmente para fins estéticos, tem atingido índices alarmantes nas últimas três décadas. Além dos efeitos desejados, uma infinidade de efeitos colaterais já foi bem descrita na literatura, como vários tipos de câncer, ginecomastia, peliosis hepatis, insuficiência renal, virilização, dentre outros. Sobre a função tireóidea, o efeito mais pronunciado em seres humanos é a diminuição da TBG, com conseqüente diminuição sérica de T3 e T4 totais, dependendo, porém, da susceptibilidade da molécula à aromatização e conseqüente transformação em estrógeno. Em ratos, o tratamento com esteróides anabolizantes altera a metabolização periférica dos hormônios tireóideos e também parece causar importante efeito proliferativo sobre as células tireóideas. Assim, o presente artigo visa rever os dados publicados acerca dos efeitos de doses suprafisiológicas de esteróides anabolizantes sobre a função tireóidea, reforçando o perigo que a utilização indiscriminada dessas drogas pode causar à saúde.

The use of anabolic steroids to increase physical performance and for aesthetic ends has reached alarming indices in the last three decades. Besides the desired actions, several collateral effects have been described in the literature, such as the development of some types of cancer, ginecomasty, peliosis hepatis, renal insufficiency, virilization, amongst others. The most proeminent effect on human thyroid function is the reduction of thyroxine binding globulin (TBG), with consequent reductions of total serum T3 and T4, depending however on the susceptibility of the drug to aromatization and subsequent transformation into estrogen. In rats, anabolic steroids also act in the peripheral metabolism of thyroid hormones and seem to exert an important proliferative effect on thyroid cells. Thus, the aim of the present paper is to review data on the effect of supraphysiological doses of anabolic steroids on thyroid function, showing the danger that indiscriminate use of these drugs can cause to health.

Type 2 Iodothyronine Deiodinase Activity and Expressions of MBP and Synapsin I in Brain of Young Rats with Iodine Deficiency and Excess / 环境与健康杂志

Objective To study the activity of type 2 Iodothyronine deiodinase(D2)and the expressions of myelin basic protein(MBP)and synapsinⅠin the brain tissue of young rats fed on a diet with different levels of iodine.Methods Wistar rats were fed on a diet with different doses of KIO_3 for 3 months and then mated randomly.The serum TH and the brain D2 activity were measured in 28 days old pups.The protein expressions of MBP and SynapsinⅠin their brains were determined by immunohistochemistry staining.Results Compared with normal iodine group(NI),the serum TH levels of low iodine group(LI) were lower,while those of iodine excess groups were gradually decreased with their increase of iodine intake,especially in 100-fold high iodine group(100 HI),TT_4 and FT_4 were significantly decreased(P0.05).The immunohistochemistry staining showed weakly positive reactivity of MBP in corpus callosum and stronger of synapsin I in hippocampus CA3 in LI group compared with NI. The similar alterations were also found in all iodine excess groups with their increase of iodine intake.But MBP reactivity was stronger in 100 HI rats than the LI ones.Conclusion Iodine deficiency and iodine excess can cause hypothyroidism in degrees in the young rats,more severe hypothyroid and retarded myelin sheath and synapses can be caused in iodine deficiency compared with iodine excess.

The Impact of Different Iodine Intakes on Type Ⅰ Iodothyronine Deiodinase Activity and mRNA Expression in Mouse Thyroid Tissue / 生物化学与生物物理进展

Thyroid function ultimately depends on appropriate iodine supply to the gland. Thyroid hormone deiodination is an intrinsic component of the thyroid hormone homeostasis. Type Ⅰ iodothyronine deiodinase (D1) plays an important role in thyroid hormone metabolism and has close relationship with thyroid function. Based on successfully establishing animal models of iodine deficiency and iodine excess in Babl/c mice (Babl/c mice were randomly divided into five groups: low iodine (LI), normal iodine (NI), five-fold iodine (5HI) , ten-fold iodine (10HI) and fifty-fold iodine (50HI) group. Three months and six months after admistration, they were sacrificed and thyroids were excised), the expression level of D1 mRNA were examined by using real time quantitative PCR method. D1 activity was analyzed by 125I-rT3 as substrate combined with ion-exchange chromatography. The thyroid hormone was measured with radioimmunoassay method. The data revealed that in the case of iodine deficiency, both D1 mRNA expression and D1 activity was greatly increased(compared with NI groups, P

ASSAY OF TYPE I IODOTHYRONINE DEIODINASE ACTIVITY AND mRNA EXPRESSION IN THYROID IN RATS OF DIFFERENT IODINE NUTRITION STATUS / 营养学报

Objective: To further investigate the effects of iodine intake on thyroid function and its possible mechanism. Method: Wistar rats were randomly divided into six groups: LI, NI, 5HI, 10HI, 50HI, 100HI. Different groups of rats were fed with feed and water of different iodine content. 3, 6 and 12 months after administration, they were sacrificed and thyroids were excised. The thyroid D1 mRNA expression level was determined by RT-PCR semi-quantitative method and the thyroid D1 activity was analyzed by using 125I-rT3 as substrate. Results: Compared with NI group, the thyroid D1 mRNA expression was decreased in all HI groups, and D1 activity was significantly higher in LI group and lower in HI groups. There was a tendency of decrease in D1 activity with increased doses of iodine intakes. Conclusion: In the case of iodine deficiency, thyroid D1 activity will increase greatly in order to convert more T4 to T3, but deficient iodine intake doesn’t improve thyroid D1 mRNA expression. Excess iodine can inhibit both thyroid D1 mRNA expression and its activity.

Thyroid Hormone Receptor Dynamics in Thyroid Hormone Response Elements of the Human Type 1 Iodothyronine Deiodinase Gene / 대한내분비학회지

BACKGROUND: Type 1 iodothyronine deiodinase (D1), the product of the hdio1 gene, is involved in thyroid hormone activation by the deiodination of thyroxine (T4) to form 3, 5, 3'-triiodothyronine (T3). Recent studies have identified two thyroid hormone response elements (TREs) in the 5 flanking region of the hdio1 gene. TRE1, proximal to TRE in the hdio1 gene, consists of a direct repeat of thyroid hormone receptor (TR) binding octamers with 10 bp separating the two TR binding sites. The upstream TRE, TRE2, is a classical direct repeat of retinoid X receptor (RXR)/TR binding half-sites with a 4-bp separation. There are few studies clarifying the TR dynamics in the TRE of a specific gene with or without the exposure of activated thyroid hormone. We evaluated TR binding patterns in the proximal and distal TREs of the hdio1 gene before and after T3 stimulation. METHODS: We employed chromatin immunoprecipitation (ChIP) technique to investigate the TR-TRE interaction before and after T3 stimulation in human hepatocellular carcinoma HepG2 cell line.Following cross-linking and sonication of the cells, immunoprecipitation was performed overnight at 4degrees C with TR 1, TR 1 and TR 2 antibodies. We analyzed the binding patterns and amounts of TR 1, TR 1 and TR 2 to TRE1 and TRE2 before and after 12 hours stimulation with 100 nM T3 by using conventional and quantitative real-time polymerase chain reactions (RQ-PCR). Reverse transcriptional PCR (RT-PCR) and Western blot with TR 1, TR 1 and TR 2 antibodies were performed to measure the levels of hdio1 mRNA and TR 1, TR 1 and TR 2 proteins before and after 12 hours exposure to 100 nM T3. RESULTS: In TRE1, TR 1 binding was significantly decreased after 12 hours stimulation with 100nM T3 (3.74-->1.97, delta=-47.3%, p3.01, delta=-71.1%, p 2.93, delta=-76.7%, p 9.84, delta=+7.3%). Total TR bindings in TRE2 were significantly decreased after 12 hours stimulation with 100 nM T3 (32.14 --> 15.78, delta=-50.9%, p<0.05). The TR bindings to TRE1 and TRE2 were not significantly different by the amounts of TR antibodies used during ChIP assays. The levels of hdio1 mRNA were significantly increased, 2.03 times, after 12 hours exposure to 100nM T3 (p<0.001). Western blot showed no significant change of the level of each TR isoform protein before and after 12 hours exposure to 100 nM T3. CONCLUSION: Our results demonstrate the dynamics of TR 1 at proximal TRE (TRE1) and the switching phenomenon of TR isoforms at distal TRE (TRE2) of the hdio1 gene after T3 stimulation. Further investigation, however, is needed to clarify the mechanisms of these observations.

Effects of Selenium on Thyroid Function and Deiodinase Activities in EAT Rats / 环境与健康杂志

Objective To explore the effects of different levels of selenium nutrition on thyroid function,liver deiodinase type Ⅰ(DⅠ) and brain deiodinase type Ⅱ(DⅡ) activities in experimental autoimmune thyroiditis (EAT) rats. Methods A total of 32 female Lewis rats were randomly divided into four groups that included control group,model group,EAT with selenium-supplementation group and EAT with selenium-deficiency group. After two weeks of the basal diet administration,the rats were fed on forage containing different levels of selenium for nine weeks and the total intake of selenium were 4,4,40 and 0.4 ?g/d,respectively. The rats of model group,EAT with selenium-supplementation group and EAT with selenium-deficiency group were induced to establish the model of experimental autoimmune thyroiditis from the third week to eighth week. The pathological change of thyroid was examined,and the levels of selenium in the blood,serum thyroid autoantibody and thyroid hormone,DⅠ and DⅡ activities were measured simultaneously. Results Compared with control group,thyroid autoantibody and thyroid hormone levels significantly increased in model group,EAT with selenium-supplementation group and EAT with selenium-deficiency group (P