H9c2 cardiomyoblasts produce thyroid hormone

2008 ◽  
Vol 294 (5) ◽  
pp. C1227-C1233 ◽  
Author(s):  
Christof Meischl ◽  
Henk P. Buermans ◽  
Thierry Hazes ◽  
Marian J. Zuidwijk ◽  
René J. P. Musters ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Peroxidase ◽  
Sodium Iodide Symporter ◽  
Hormone Synthesis ◽  
Cardiovascular Hemodynamics ◽  
Wide Range ◽  
Vitro Model

Thyroid hormone acts on a wide range of tissues. In the cardiovascular system, thyroid hormone is an important regulator of cardiac function and cardiovascular hemodynamics. Although some early reports in the literature suggested an unknown extrathyroidal source of thyroid hormone, it is currently thought to be produced exclusively in the thyroid gland, a highly specialized organ with the sole function of generating, storing, and secreting thyroid hormone. Whereas most of the proteins necessary for thyroid hormone synthesis are thought to be expressed exclusively in the thyroid gland, we now have found evidence that all of these proteins, i.e., thyroglobulin, DUOX1, DUOX2, the sodium-iodide symporter, pendrin, thyroid peroxidase, and thyroid-stimulating hormone receptor, are also expressed in cardiomyocytes. Furthermore, we found thyroglobulin to be transiently upregulated in an in vitro model of ischemia. When performing these experiments in the presence of 125I, we found that 125I was integrated into thyroglobulin and that under ischemia-like conditions the radioactive signal in thyroglobulin was reduced. Concomitantly we observed an increase of intracellularly produced, 125I-labeled thyroid hormone. In conclusion, our findings demonstrate for the first time that cardiomyocytes produce thyroid hormone in a manner adapted to the cell's environment.

Iodide Metabolism and Effects

2020 ◽  
pp. 25-33
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Thyroid Hormones ◽  
Dietary Supplement ◽  
Thyroid Function ◽  
Thyroid Stimulating Hormone ◽  
Hormone Synthesis ◽  
Serum Tsh ◽  
Tsh Stimulation ◽  
Sensitive Marker

Iodine (I2) is essential in the synthesis of thyroid hormones T4 and T3 and functioning of the thyroid gland. Both T3 and T4 are metabolically active, but T3 is four times more potent than T4. Our body contains 20-30 mg of I2, which is mainly stored in the thyroid gland. Iodine is naturally present in some foods, added to others, and available as a dietary supplement. Serum thyroid stimulating hormone (TSH) level is a sensitive marker of thyroid function. Serum TSH is increased in hypothyroidism as in Hashimoto's thyroiditis. In addition to regulation of thyroid function, TSH promotes thyroid growth. If thyroid hormone synthesis is chronically impaired, TSH stimulation eventually may lead to the development of a goiter. This chapter explores the iodide metabolism and effects of Hashimoto's disease.

scholarly journals Central Hypothyroidism Due to a TRHR Mutation Causing Impaired Ligand Affinity and Transactivation of Gq

2017 ◽  
Vol 102 (7) ◽  
pp. 2433-2442 ◽  
Author(s):  
Marta García ◽  
Jesús González de Buitrago ◽  
Mireia Jiménez-Rosés ◽  
Leonardo Pardo ◽  
Patricia M. Hinkle ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Molecular Mechanisms ◽  
Pituitary Hormones ◽  
Thyroid Stimulating Hormone ◽  
Consanguineous Family ◽  
Intracellular Loop ◽  
Central Hypothyroidism ◽  
Hormone Synthesis ◽  
Half Maximal Effective Concentration

Abstract Context: Central congenital hypothyroidism (CCH) is an underdiagnosed disorder characterized by deficient production and bioactivity of thyroid-stimulating hormone (TSH) leading to low thyroid hormone synthesis. Thyrotropin-releasing hormone (TRH) receptor (TRHR) defects are rare recessive disorders usually associated with incidentally identified CCH and short stature in childhood. Objectives: Clinical and genetic characterization of a consanguineous family of Roma origin with central hypothyroidism and identification of underlying molecular mechanisms. Design: All family members were phenotyped with thyroid hormone profiles, pituitary magnetic resonance imaging, TRH tests, and dynamic tests for other pituitary hormones. Candidate TRH, TRHR, TSHB, and IGSF1 genes were screened for mutations. A mutant TRHR was characterized in vitro and by molecular modeling. Results: A homozygous missense mutation in TRHR (c.392T > C; p.I131T) was identified in an 8-year-old boy with moderate hypothyroidism (TSH: 2.61 mIU/L, Normal: 0.27 to 4.2; free thyroxine: 9.52 pmol/L, Normal: 10.9 to 25.7) who was overweight (body mass index: 20.4 kg/m2, p91) but had normal stature (122 cm; –0.58 standard deviation). His mother, two brothers, and grandmother were heterozygous for the mutation with isolated hyperthyrotropinemia (TSH: 4.3 to 8 mIU/L). The I131T mutation, in TRHR intracellular loop 2, decreases TRH affinity and increases the half-maximal effective concentration for signaling. Modeling of TRHR-Gq complexes predicts that the mutation disrupts the interaction between receptor and a hydrophobic pocket formed by Gq. Conclusions: A unique missense TRHR defect identified in a consanguineous family is associated with central hypothyroidism in homozygotes and hyperthyrotropinemia in heterozygotes, suggesting compensatory elevation of TSH with reduced biopotency. The I131T mutation decreases TRH binding and TRHR-Gq coupling and signaling.

Effects of a selenium deficient diet on thyroid function of normal and perchlorate treated rats

1988 ◽  
Vol 118 (4) ◽  
pp. 495-502 ◽  
Author(s):  
J. Golstein ◽  
B. Corvilain ◽  
F. Lamy ◽  
D. Paquer ◽  
J. E. Dumont
Keyword(s):  
Thyroid Hormone ◽  
Tap Water ◽  
Selenium Deficiency ◽  
Thyroid Peroxidase ◽  
Deficient Diet ◽  
Adult Rats ◽  
Pregnant Rats ◽  
Hormone Synthesis ◽  
Thyroid Hormone Synthesis

Abstract. Pregnant rats were submitted to a selenium-deficient diet immediately after mating; it was continued for 4 weeks after delivery. The pups were sacrificed at 3 and 4 weeks of age. Perchlorate, an antithyroid agent inhibiting iodide trapping in the thyroid, was administered via the drinking water to half of the rats. Rats submitted to a normal laboratory diet and to the experimental diet supplemented with selenium were used as controls. The effects of selenium deficiency were an increase in the number of growth abnormalities, growth retardation, and decreased seleno-dependent glutathione peroxidase (GSH-Px) activity in plasma and in various organs. These effects were relieved by selenium supplementation in the diet. Perchlorate treatment induced the classic picture of primary hypothyroidism. Selenium deficiency increased thyroid hormone levels in perchlorate-treated rats and in controls drinking tap water. In the latter group, it also decreased TSH plasma concentration and thyroid weight. These effects were partially reversed by Se supplementation. In vitro experiments, performed on adult rats, revealed increased radioiodide uptake and organification in glands from the rats submitted to the selenium-free diet. Plasma T3 half-life was similar in control and Se-deficient rats. These data suggest a higher efficiency of thyroid hormone synthesis in the thyroids of selenium-deficient rats, despite a lower thyroid stimulation as evaluated by serum TSH. They are compatible with the hypothesis that decreased selenium supply, leading to a decreased GSH-Px in the thyroid, increases hydrogen peroxide steady state level and thus thyroid peroxidase activity and thyroid hormone synthesis.

scholarly journals Resveratrol Alleviates the Inhibitory Effect of Tunicamycin-Induced Endoplasmic Reticulum Stress on Expression of Genes Involved in Thyroid Hormone Synthesis in FRTL-5 Thyrocytes

2021 ◽  
Vol 22 (9) ◽  
pp. 4373
Author(s):  
Gaiping Wen ◽  
Klaus Eder ◽  
Robert Ringseis
Keyword(s):  
Transcription Factor ◽  
Thyroid Hormone ◽  
Er Stress ◽  
Combined Treatment ◽  
Thyroid Peroxidase ◽  
Sodium Iodide Symporter ◽  
Hormone Synthesis ◽  
Thyroid Hormone Synthesis ◽  
Expression Of Genes ◽  
Thyroid Transcription Factor

Recently, ER stress induced by tunicamycin (TM) was reported to inhibit the expression of key genes involved in thyroid hormone synthesis, such as sodium/iodide symporter (NIS), thyroid peroxidase (TPO) and thyroglobulin (TG), and their regulators such as thyrotropin receptor (TSHR), thyroid transcription factor-1 (TTF-1), thyroid transcription factor-2 (TTF-2) and paired box gene 8 (PAX-8), in FRTL-5 thyrocytes. The present study tested the hypothesis that resveratrol (RSV) alleviates this effect of TM in FRTL-5 cells. While treatment of FRTL-5 cells with TM alone (0.1 µg/mL) for 48 h strongly induced the ER stress-sensitive genes heat shock protein family A member 5 (HSPA5) and DNA damage inducible transcript 3 (DDIT3) and repressed NIS, TPO, TG, TSHR, TTF-1, TTF-2 and PAX-8, combined treatment with TM (0.1 µg/mL) and RSV (10 µM) for 48 h attenuated this effect of TM. In conclusion, RSV alleviates TM-induced ER stress and attenuates the strong impairment of expression of genes involved in thyroid hormone synthesis and their regulators in FRTL-5 thyrocytes exposed to TM-induced ER stress. Thus, RSV may be useful for the treatment of specific thyroid disorders, provided that strategies with improved oral bioavailability of RSV are applied.

Cognitive and Behavioral Complications of Congenital Hypothyroidism

2010 ◽  
Author(s):  
Ruth D. Nass
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Brain Development ◽  
Congenital Hypothyroidism ◽  
Behavioral Problems ◽  
Thyroid Stimulating Hormone ◽  
Primary Hypothyroidism ◽  
Normal Brain ◽  
Gene Encoding ◽  
Hormone Synthesis

Congenital hypothyroidism (CH) affects approximately 1 in 3,500 newborns. There is a female preponderance. In areas of iodine insufficiency, the incidence is higher, since iodine is a key element in the synthesis of thyroid hormone. Approximately 85% of CH cases are sporadic, whereas 15% are hereditary. Thyroid hormone is essential for normal pre- and postnatal brain development. The importance of in utero thyroid hormone status is demonstrated by the fact that maternal hypothyroidism during pregnancy is known to result in cognitive and motor deficits in the offspring (Forrest 2004; Zoeller and Rovet 2004). Congenital hypothyroidism is already expressed in fetal life; maternal T4, transferred via the placenta, is not sufficient for normal brain development (Forrest 2004; Haddow et al. 1999; Opazo et al. 2008; Pop and Vulsma 2005). Prior to newborn screening, CH that went undiagnosed and untreated for more than 3 months was associated with permanent and significant mental retardation, as well as behavioral problems. Outcome is now significantly better. Children with CH have normal intelligence, although subtle and specific cognitive and behavioral problems occur. Congenital hypothyroidism can be caused by primary hypothyroidism, due to a defect of the thyroid gland, or by central hypothyroidism secondary to defective hypothalamic or pituitary regulation of thyroid hormone. Several types of primary thyroid abnormalities may occur. Thyroid dysgenesis is the result of a missing, ectopic, or hypoplastic gland. Proteins that are crucial for normal thyroid gland development include the thyroid transcription factors PAX8, TTF1, TTF2, FOXE1 and the thyroid stimulating hormone (TSH) receptor gene. Thyroid dyshormonogenesis is generally due to an autosomal recessive genetic defect in any of many stages of thyroid hormone synthesis, secretion and transport (Moreno and Visser 2007). One in 50,000 children has autosomal dominant thyroid hormone resistance (RTH) due to a mutation in the gene encoding for the TRb thyroid receptors (Hauser et al. 1993; Weiss et al. 1993). Iodine deficiency can also cause CH (endemic cretinism) (DeLange et al. 2000). Gaudino and colleagues (2005) determined the etiology of CH in 49 non-athyroid cases.

scholarly journals Glycosylation in the Thyroid Gland: Vital Aspects of Glycoprotein Function in Thyrocyte Physiology and Thyroid Disorders

2018 ◽  
Vol 19 (9) ◽  
pp. 2792 ◽  
Author(s):  
Marta Ząbczyńska ◽  
Kamila Kozłowska ◽  
Ewa Pocheć
Keyword(s):  
Thyroid Gland ◽  
Thyroid Hormones ◽  
Thyroid Autoimmunity ◽  
Thyroid Stimulating Hormone ◽  
Pathological Process ◽  
Metabolic Clearance ◽  
Sodium Iodide Symporter ◽  
Hormone Synthesis ◽  
Iodide Transport

The key proteins responsible for hormone synthesis in the thyroid are glycosylated. Oligosaccharides strongly affect the function of glycosylated proteins. Both thyroid-stimulating hormone (TSH) secreted by the pituitary gland and TSH receptors on the surface of thyrocytes contain N-glycans, which are crucial to their proper activity. Thyroglobulin (Tg), the protein backbone for synthesis of thyroid hormones, is a heavily N-glycosylated protein, containing 20 putative N-glycosylated sites. N-oligosaccharides play a role in Tg transport into the follicular lumen, where thyroid hormones are produced, and into thyrocytes, where hyposialylated Tg is degraded. N-glycans of the cell membrane transporters sodium/iodide symporter and pendrin are necessary for iodide transport. Some changes in glycosylation result in abnormal activity of the thyroid and alteration of the metabolic clearance rate of hormones. Alteration of glycan structures is a pathological process related to the progression of chronic diseases such as thyroid cancers and autoimmunity. Thyroid carcinogenesis is accompanied by changes in sialylation and fucosylation, β1,6-branching of glycans, the content and structure of poly-LacNAc chains, as well as O-GlcNAcylation, while in thyroid autoimmunity the main processes affected are sialylation and fucosylation. The glycobiology of the thyroid gland is an intensively studied field of research, providing new data helpful in understanding the role of the sugar component in thyroid protein biology and disorders.

scholarly journals Effects of 99mTc on the electrochemical properties of thiamazole in vitro

2021 ◽  
Vol 40 (1) ◽  
pp. 21
Author(s):  
Safija Herenda ◽  
Anera Kazlagić ◽  
Edhem Hasković ◽  
Jelena Šćepanović ◽  
Jasmina Marušić
Keyword(s):  
Cyclic Voltammetry ◽  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Cyclic Voltammograms ◽  
Reduction Peak ◽  
Hormone Synthesis ◽  
Reduction Peak Current ◽  
Sodium Pertechnetate ◽  
99Mtc Activity

Thiamazole inhibits the thyroid hormone synthesis and does not inactivate the existing thyroxine and triiodothyronine that circulate in the blood. In this paper Thiamazole electrochemical behavior was monitored by cyclic voltammetry on glassy carbon (GC) electrode in the absence and presence of sodium pertechnetate (99mTc). The influence of different Thiamazole concentrations without and in the presence of radiopharmaceutical 99mTc, the effect of the number of scan cycles, and the effect of 99mTc activity on the appearance of cyclic voltammograms were examined. The results show that there is an observed increase in the reduction peak current with an increase of Thiamazole concentration. It was found that the concentration of the tested drug had a significant effect on its redox characteristics. The results obtained show that the application of different concentrations of sodium pertechnetate exhibits the inhibitory properties of the used radiopharmaceutical on the drug in the treatment of thyroid gland disease.

Phenotypic Variability of Patients With PAX8 Variants Presenting With Congenital Hypothyroidism and Eutopic Thyroid

2020 ◽  
Vol 106 (1) ◽  
pp. e152-e170
Author(s):  
Núria Camats ◽  
Noelia Baz-Redón ◽  
Mónica Fernández-Cancio ◽  
María Clemente ◽  
Ariadna Campos-Martorell ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Congenital Hypothyroidism ◽  
Phenotypic Variability ◽  
Hereditary Diseases ◽  
Hormone Synthesis ◽  
Functional Studies ◽  
Thyroid Hormone Synthesis ◽  
Thyroid Dyshormonogenesis

Abstract Purpose Thyroid dyshormonogenesis is a heterogeneous group of hereditary diseases produced by a total/partial blockage of the biochemical processes of thyroid-hormone synthesis and secretion. Paired box 8 (PAX8) is essential for thyroid morphogenesis and thyroid hormone synthesis. We aimed to identify PAX8 variants in patients with thyroid dyshormonogenesis and to analyze them with in vitro functional studies. Patients and Methods Nine pediatric patients with a eutopic thyroid gland were analyzed by the Catalan screening program for congenital hypothyroidism. Scintigraphies showed absent, low, or normal uptake. Only one patient had a hypoplastic gland. On reevaluation, perchlorate discharge test was negative or compatible with partial iodine-organization deficit. After evaluation, 8 patients showed permanent mild or severe hypothyroidism. Massive-sequencing techniques were used to detect variants in congenital hypothyroidism-related genes. In vitro functional studies were based on transactivating activity of mutant PAX8 on a TG-gene promoter and analyzed by a dual-luciferase assays. Results We identified 7 heterozygous PAX8 exonic variants and 1 homozygous PAX8 splicing variant in 9 patients with variable phenotypes of thyroid dyshormonogenesis. Five were novel and 5 variants showed a statistically significant impaired transcriptional activity of TG promoter: 51% to 78% vs the wild type. Conclusions Nine patients presented with PAX8 candidate variants. All presented with a eutopic thyroid gland and 7 had deleterious variants. The phenotype of affected patients varies considerably, even within the same family; but, all except the homozygous patient presented with a normal eutopic thyroid gland and thyroid dyshormonogenesis. PAX8 functional studies have shown that 6 PAX8 variants are deleterious. Our studies have proven effective in evaluating these variants.

Auto-Regulation of the Thyroid Gland Beyond Classical Pathways

2020 ◽  
Vol 128 (06/07) ◽  
pp. 437-445 ◽  
Author(s):  
Klaudia Brix ◽  
Joanna Szumska ◽  
Jonas Weber ◽  
Maria Qatato ◽  
Vaishnavi Venugopalan ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Hormone Receptors ◽  
Self Regulation ◽  
Thyroid Stimulating Hormone ◽  
Apical Plasma Membrane ◽  
Deficient Mice ◽  
Stimulating Hormone

AbstractThis mini-review asks how self-regulation of the thyroid gland is realized at the cellular and molecular levels by canonical and non-canonical means. Canonical pathways of thyroid regulation comprise thyroid stimulating hormone-triggered receptor signaling. As part of non-canonical regulation, we hypothesized an interplay between protease-mediated thyroglobulin processing and thyroid hormone release into the circulation by means of thyroid hormone transporters like Mct8. We proposed a sensing mechanism by different thyroid hormone transporters, present in specific subcellular locations of thyroid epithelial cells, selectively monitoring individual steps of thyroglobulin processing, and thus, the cellular thyroid hormone status. Indeed, we found that proteases and thyroid hormone transporters are functionally inter-connected, however, in a counter-intuitive manner fostering self-thyrotoxicity in particular in Mct8- and/or Mct10-deficient mice. Furthermore, the possible role of the G protein-coupled receptor Taar1 is discussed, because we detected Taar1 at cilia of the apical plasma membrane of thyrocytes in vitro and in situ. Eventually, through pheno-typing Taar1-deficient mice, we identified a co-regulatory role of Taar1 and the thyroid stimulating hormone receptors. Recently, we showed that inhibition of thyroglobulin-processing enzymes results in disappearance of cilia from the apical pole of thyrocytes, while Taar1 is re-located to the endoplasmic reticulum. This pathway features a connection between thyrotropin-stimulated secretion of proteases into the thyroid follicle lumen and substrate-mediated self-assisted control of initially peri-cellular thyroglobulin processing, before its reinternalization by endocytosis, followed by extensive endo-lysosomal liberation of thyroid hormones, which are then released from thyroid follicles by means of thyroid hormone transporters.

scholarly journals Bioinorganic Chemistry in Thyroid Gland: Effect of Antithyroid Drugs on Peroxidase-Catalyzed Oxidation and Iodination Reactions

2006 ◽  
Vol 2006 ◽  
pp. 1-9 ◽  
Author(s):  
Gouriprasanna Roy ◽  
G. Mugesh
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Gland ◽  
Bioinorganic Chemistry ◽  
Antithyroid Drugs ◽  
Thyroid Peroxidase ◽  
Current Interest ◽  
Hormone Synthesis ◽  
Thyroid Hormone Synthesis ◽  
Interesting Compound ◽  
Catalyzed Oxidation

Propylthiouracil (PTU) and methimazole (MMI) are the most commonly used antithyroid drugs. The available data suggest that these drugs may block the thyroid hormone synthesis by inhibiting the thyroid peroxidase (TPO) or diverting oxidized iodides away from thyroglobulin. It is also known that PTU inhibits the selenocysteine-containing enzyme ID-1 by reacting with the selenenyl iodide intermediate (E-SeI). In view of the current interest in antithyroid drugs, we have recently carried out biomimetic studies to understand the mechanism by which the antithyroid drugs inhibit the thyroid hormone synthesis and found that the replacement of sulfur with selenium in MMI leads to an interesting compound that may reversibly block the thyroid hormone synthesis. Our recent results on the inhibition of lactoperoxidase (LPO)-catalyzed oxidation and iodination reactions by antithyroid drugs are described.

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