Thyroid hormones (THs) are secreted by the thyroid gland. They control lipid, carbohydrate, and protein metabolism, heart rate, neural development, as well as cardiovascular, renal, and brain functions. The thyroid gland mainly produces l-thyroxine (T4) as a prohormone, and 5'-deiodination of T4 by iodothyronine deiodinases generates the nuclear receptor binding hormone T3. In this Review, we discuss the basic aspects of the chemistry and biology as well as recent advances in the biosynthesis of THs in the thyroid gland, plasma transport, and internalization of THs in their target organs, in addition to the deiodination and various other enzyme-mediated metabolic pathways of THs. We also discuss thyroid hormone receptors and their mechanism of action to regulate gene expression, as well as various thyroid-related disorders and the available treatments.
Coordination behaviour of antithyroid drugs against the Fe(I)(NO)2 group in solution: ESR and FT-NMR study
Raised total thyroxine and free thyroxine index but normal free thyroxine. A serum abnormality due to inherited increased affinity of iodothyronines for serum binding protein
Phenolic and nonphenolic ring deiodinations of iodothyronines in cultured hepatocarcinoma cell homogenate from monkey
Formation and metabolism of 3',5'-diiodothyronine and 3,5-diiodothyronine by cultured monkey hepatocarcinoma cells
Triiodothyronine, thyroxine, and iodine in purified thyroglobulin from patients with Graves' disease
Structure of prealbumin: secondary, tertiary and quaternary interactions determined by Fourier refinement at 1.8 A
The irreversible inactivation of thyroid peroxidase by methylmercaptoimidazole, thiouracil, and propylthiouracil in vitro and its relationship to in vivo findings
Analysis of thyroid hormone binding to human serum prealbumin by 8-anilinonaphthalene-1-sulfonate fluorescence
Kinetics of thyroglobulin iodination and of hormone synthesis catalysed by thyroid peroxidase. Role of iodide in the coupling reaction
Negative cooperativity in the binding of thyroxine to human serum prealbumin. Preparation of tritium-labeled 8-anilino-1-naphthalenesulfonic acid
Substitution of cysteine for selenocysteine in type I iodothyronine deiodinase reduces the catalytic efficiency of the protein but enhances its translation
Deiodination and deconjugation of the glucuronide conjugates of the thyroid hormones by rat liver and brain microsomes
Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors
Hormone formation in the isolated fragment 1-171 of human thyroglobulin involves the couple tyrosine 5 and tyrosine 130
Thyroxine and 3,3',5-triiodothyronine are glucuronidated in rat liver by different uridine diphosphate-glucuronyltransferases
Administration of thyroxine in treated Graves' disease. Effects on the level of antibodies to thyroid-stimulating hormone receptors and on the risk of recurrence of hyperthyroidism
Binding of 3,5,3'-triiodothyronine (T3) and its analogs to the in vitro translational products of c-erbA protooncogenes: differences in the affinity of the alpha- and beta-forms for the acetic acid analog and failure of the human testis and kidney alpha-2 products to bind T3
Metabolism of triiodothyroacetic acid (TA3) in rat liver. I. Deiodination of TA3 and TA3 sulfate by microsomes
Human myeloperoxidase and thyroid peroxidase, two enzymes with separate and distinct physiological functions, are evolutionarily related members of the same gene family
Porcine thyroid peroxidase: relationship between the native enzyme and an active, highly purified tryptic fragment
Crystal structure of phlorizin and the iodothyronine deiodinase inhibitory activity of phloretin analogues
Peroxidatic degradation and ether link cleavage of thyroxine in a particulate fraction of human thyroid
Substrate cycling between gluconeogenesis and glycolysis in euthyroid, hypothyroid, and hyperthyroid man
Deiodination of L-thyroxine and its activity on the oxidation in vitro of reduced nicotinamide-adenine dinucleotide by peroxidase plus hydrogen peroxide
3'-Monoiodothyronine degradation in rat liver homogenate: enzyme characteristics and documentation of deiodination by high-pressure liquid chromatography
Successful treatment of hyperthyroidism due to nonneoplastic pituitary TSH hypersecretion with 3,5,3'-triiodothyroacetic acid (TRIAC)
Ether link cleavage is the major pathway of iodothyronine metabolism in the phagocytosing human leukocyte and also occurs in vivo in the rat
Metabolism of 3,3'-Diiodothyronine and 3'-monoiodothyronine, and effect of potassium cyanide and dinitrophenol and glucuronidation of thyroxine in cultured rat hepatoma cells
Triiodothyronine treatment increases substrate cycling between pyruvate carboxylase and malic enzyme in perfused rat liver
The selenium analog of methimazole. Measurement of its inhibitory effect on type I 5'-deiodinase and of its antithyroid activity
Effect of 3,5,3'-Triiodothyronine (T3) administration on dio1 gene expression and T3 metabolism in normal and type 1 deiodinase-deficient mice
Importance of the content and localization of tyrosine residues for thyroxine formation within the N-terminal part of human thyroglobulin
Resistance to thyroid hormone in subjects from two unrelated families is associated with a point mutation in the thyroid hormone receptor beta gene resulting in the replacement of the normal proline 453 with serine
The selenium analog of 6-propylthiouracil. Measurement of its inhibitory effect on type I iodothyronine deiodinase and of its antithyroid activity
Evidence for a radical mechanism in peroxidase-catalyzed coupling. I. Steady-state experiments with various peroxidases
Uptake of triiodothyroacetic acid and its effect on thyrotropin secretion in cultured anterior pituitary cells
Glucuronidation of thyroid hormone by human bilirubin and phenol UDP-glucuronyltransferase isoenzymes
An everted repeat mediates retinoic acid induction of the gamma F-crystallin gene: evidence of a direct role for retinoids in lens development
Screening for mutations of the human thyroid peroxidase gene in patients with congenital hypothyroidism
Sulfation and sulfotransferases. Introduction: changing view of sulfation and the cytosolic sulfotransferases
Autocatalytic processing of heme by lactoperoxidase produces the native protein-bound prosthetic group.
Amyloid fibril formation and protein misassembly: a structural quest for insights into amyloid and prion diseases
Purification, molecular cloning, and functional expression of the human nicodinamide-adenine dinucleotide phosphate-regulated thyroid hormone-binding protein
Clinical and hormonal outcome after two years of triiodothyroacetic acid treatment in a child with thyroid hormone resistance
N-linked glycosylation of the thyroid Na+/I- symporter (NIS). Implications for its secondary structure model.
Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cdnas
X-ray crystal structure and characterization of halide-binding sites of human myeloperoxidase at 1.8 A resolution
In vitro effect of Triac on resistance to thyroid hormone receptor mutants: potential basis for therapy
Structure of a new polymorphic monoclinic form of human transthyretin at 3 A resolution reveals a mixed complex between unliganded and T4-bound tetramers of TTR
Structure of rat transthyretin (rTTR) complex with thyroxine at 2.5 A resolution: first non-biased insight into thyroxine binding reveals different hormone orientation in two binding sites
Tyrosine cross-linking of extracellular matrix is catalyzed by Duox, a multidomain oxidase/peroxidase with homology to the phagocyte oxidase subunit gp91phox
Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases
Loop variants of the serpin thyroxine-binding globulin: implications for hormone release upon limited proteolysis
Biomimetic studies on iodothyronine deiodinase intermediates: modeling the reduction of selenenyl iodide by thiols
Identification of a truncated dual oxidase 2 (DUOX2) messenger ribonucleic acid (mRNA) in two rat thyroid cell lines. Insulin and forskolin regulation of DUOX2 mRNA levels in FRTL-5 cells and porcine thyrocytes
Effect of iodide on nicotinamide adenine dinucleotide phosphate oxidase activity and Duox2 protein expression in isolated porcine thyroid follicles
Substitution of cysteine for selenocysteine in the catalytic center of type III iodothyronine deiodinase reduces catalytic efficiency and alters substrate preference
The iodothyronine selenodeiodinases are thioredoxin-fold family proteins containing a glycoside hydrolase clan GH-A-like structure.
Selective thyroid hormone receptor-beta activation: a strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability
Comparative efficacy and side effects of the treatment of euthyroid goiter with levo-thyroxine or triiodothyroacetic acid
A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene
Effects of the thyroid hormone receptor agonist GC-1 on metabolic rate and cholesterol in rats and primates: selective actions relative to 3,5,3'-triiodo-L-thyronine
Functional characterization of pendrin in a polarized cell system. Evidence for pendrin-mediated apical iodide efflux
Structural and functional characterization of the two human ThOX/Duox genes and their 5'-flanking regions
High resolution crystal structures of piscine transthyretin reveal different binding modes for triiodothyronine and thyroxine.
Comparison of the effects of 3,5,3'-triiodothyroacetic Acid and triiodothyronine on goiter prevention and involution and on hepatic and skeletal parameters in rats
Structures of human transthyretin complexed with thyroxine at 2.0 A resolution and 3',5'-dinitro-N-acetyl-L-thyronine at 2.2 A resolution
A 36-year retrospective analysis of the efficacy and safety of radioactive iodine in treating young Graves' patients
Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation
Endoproteolytic cleavage of human thyroperoxidase: role of the propeptide in the protein folding process
The type 2 deiodinase A/G (Thr92Ala) polymorphism is associated with decreased enzyme velocity and increased insulin resistance in patients with type 2 diabetes mellitus
Selective thyroid receptor modulation by GC-1 reduces serum lipids and stimulates steps of reverse cholesterol transport in euthyroid mice
Differential regulation of dual NADPH oxidases/peroxidases, Duox1 and Duox2, by Th1 and Th2 cytokines in respiratory tract epithelium
Anti-thyroid drugs and thyroid hormone synthesis: effect of methimazole derivatives on peroxidase-catalyzed reactions
CRYM mutations cause deafness through thyroid hormone binding properties in the fibrocytes of the cochlea
Structural rearrangements in the thyroid hormone receptor hinge domain and their putative role in the receptor function
Duox expression and related H2O2 measurement in mouse thyroid: onset in embryonic development and regulation by TSH in adult
Sources of circulating 3,5,3'-triiodothyronine in hyperthyroidism estimated after blocking of type 1 and type 2 iodothyronine deiodinases
Thyroid hormone receptor beta-specific agonist GC-1 increases energy expenditure and prevents fat-mass accumulation in rats
Ubiquitination-induced conformational change within the deiodinase dimer is a switch regulating enzyme activity
Negative feedback regulation of hypophysiotropic thyrotropin-releasing hormone (TRH) synthesizing neurons: role of neuronal afferents and type 2 deiodinase
Novel thyroxine derivatives, thyronamine and 3-iodothyronamine, induce transient hypothermia and marked neuroprotection against stroke injury
Targeting thyroid hormone receptor-beta agonists to the liver reduces cholesterol and triglycerides and improves the therapeutic index
Effects of long-term oral administration of levothyroxine sodium on glucose dynamics in healthy adult horses
Radioiodine therapy (RAI) for Graves' disease (GD) and the effect on ophthalmopathy: a systematic review
Anti-obesity, anti-diabetic, and lipid lowering effects of the thyroid receptor beta subtype selective agonist KB-141
Antithyroid drug carbimazole and its analogues: synthesis and inhibition of peroxidase-catalyzed iodination of L-tyrosine
Reduction of hepatic steatosis in rats and mice after treatment with a liver-targeted thyroid hormone receptor agonist
Activation of dual oxidases Duox1 and Duox2: differential regulation mediated by camp-dependent protein kinase and protein kinase C-dependent phosphorylation
Crystal structure of iodotyrosine deiodinase, a novel flavoprotein responsible for iodide salvage in thyroid glands
Caenorhabditis elegans and human dual oxidase 1 (DUOX1) "peroxidase" domains: insights into heme binding and catalytic activity
Neuronal 3',3,5-triiodothyronine (T3) uptake and behavioral phenotype of mice deficient in Mct8, the neuronal T3 transporter mutated in Allan-Herndon-Dudley syndrome
Thyroid peroxidase forms thionamide-sensitive homodimers: relevance for immunomodulation of thyroid autoimmunity
Expression of uncoupling protein 1 in mouse brown adipose tissue is thyroid hormone receptor-beta isoform specific and required for adaptive thermogenesis
Modeling of the 5'-deiodination of thyroxine by iodothyronine deiodinase: chemical corroboration of a selenenyl iodide intermediate
Adaptations of the autonomous nervous system controlling heart rate are impaired by a mutant thyroid hormone receptor-alpha1
Genetics and phenomics of hypothyroidism and goiter due to iodotyrosine deiodinase (DEHAL1) gene mutations
Essential molecular determinants for thyroid hormone transport and first structural implications for monocarboxylate transporter 8.
TRbeta is the critical thyroid hormone receptor isoform in T3-induced proliferation of hepatocytes and pancreatic acinar cells
Inhibition of the type 2 iodothyronine deiodinase underlies the elevated plasma TSH associated with amiodarone treatment
Halogenated phenolic contaminants inhibit the in vitro activity of the thyroid-regulating deiodinases in human liver
Deiodination of thyroid hormones by iodothyronine deiodinase mimics: does an increase in the reactivity alter the regioselectivity?
Monocarboxylate transporter 8 deficiency: altered thyroid morphology and persistent high triiodothyronine/thyroxine ratio after thyroidectomy
Insights into molecular properties of the human monocarboxylate transporter 8 by combining functional with structural information
Regioselective deiodination of thyroxine by iodothyronine deiodinase mimics: an unusual mechanistic pathway involving cooperative chalcogen and halogen bonding
Thyroid function is maintained despite increased oxidative stress in mice lacking selenoprotein biosynthesis in thyroid epithelial cells
Identification of iopanoic acid as substrate of type 1 deiodinase by a novel nonradioactive iodide-release assay
Selective thyromimetics using receptor and tissue selectivity approaches: prospects for dyslipidemia
Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade
Histidines in potential substrate recognition sites affect thyroid hormone transport by monocarboxylate transporter 8 (MCT8)
A redundant role of human thyroid peroxidase propeptide for cellular, enzymatic, and immunological activity
Structure-activity relationships of 44 halogenated compounds for iodotyrosine deiodinase-inhibitory activity
Mutations in the Pendred Syndrome (PDS/SLC26A) gene: an increasingly complex phenotypic spectrum from goiter to thyroid hypoplasia
A novel mutation in the Albumin gene (R218S) causing familial dysalbuminemic hyperthyroxinemia in a family of Bangladeshi extraction
Administration of 3,5-diiodothyronine (3,5-T2) causes central hypothyroidism and stimulates thyroid-sensitive tissues
Se- and s-based thiouracil and methimazole analogues exert different inhibitory mechanisms on type 1 and type 2 deiodinases
Crystal structure of mammalian selenocysteine-dependent iodothyronine deiodinase suggests a peroxiredoxin-like catalytic mechanism
Regioselective deiodination of iodothyronamines, endogenous thyroid hormone derivatives, by deiodinase mimics
Mutations of the thyroid hormone transporter MCT8 cause prenatal brain damage and persistent hypomyelination
3,5-Diiodo-L-thyronine (3,5-t2) exerts thyromimetic effects on hypothalamus-pituitary-thyroid axis, body composition, and energy metabolism in male diet-induced obese mice
In vitro and mouse studies supporting therapeutic utility of triiodothyroacetic acid in MCT8 deficiency
Halogen bonding controls the regioselectivity of the deiodination of thyroid hormones and their sulfate analogues
Remarkable effect of chalcogen substitution on an enzyme mimetic for deiodination of thyroid hormones
Selenium-Mediated Dehalogenation of Halogenated Nucleosides and its Relevance to the DNA Repair Pathway
Efficient Activation of Pathogenic ΔPhe501 Mutation in Monocarboxylate Transporter 8 by Chemical and Pharmacological Chaperones
Activated Thyroid Hormone Promotes Differentiation and Chemotherapeutic Sensitization of Colorectal Cancer Stem Cells by Regulating Wnt and BMP4 Signaling
Reactions of Organoselenenyl Iodides with Thiouracil Drugs: An Enzyme Mimetic Study on the Inhibition of Iodothyronine Deiodinase
Structural aspects of thyroid hormone binding to proteins and competitive interactions with natural and synthetic compounds
Halogen-Bonding Interactions of Polybrominated Diphenyl Ethers and Thyroid Hormone Derivatives: A Potential Mechanism for the Inhibition of Iodothyronine Deiodinase
A post-publication analysis of the idealized upper reference value of 2.5 mIU/L for TSH: Time to support the thyroid axis with magnesium and iron especially in the setting of reproduction medicine
Electronic and Ligand Properties of Skeletally Substituted Cyclic (Alkyl)(Amino)Carbenes (CAACs) and Their Reactivity towards Small Molecule Activation: A Theoretical Study
Biomimetic deiodination of thyroid hormones and iodothyronamines - a structure-activity relationship study
GLIS3 is indispensable for TSH/TSHR-dependent thyroid hormone biosynthesis and follicular cell proliferation
The Remarkable Effect of Halogen Substitution on the Membrane Transport of Fluorescent Molecules in Living Cells
Antigen-responsive fluorescent antibody probes generated by selective N-terminal modification of IgGs
Effects of different exercise loads on the thyroid hormone levels and serum lipid profile in swimmers.
Halogen-Mediated Membrane Transport: An Efficient Strategy for the Enhancement of Cellular Uptake of Synthetic Molecules
Thyroid Hormones Are Transport Substrates and Transcriptional Regulators of Organic Anion Transporting Polypeptide 2B1
Halogen Bonding Increases the Potency and Isozyme Selectivity of Protein Arginine Deiminase 1 Inhibitors
Halogen Bonding in Biomimetic Deiodination of Thyroid Hormones and their Metabolites and Dehalogenation of Halogenated Nucleosides
Application of principal component analysis and logistic regression model in lupus nephritis patients with clinical hypothyroidism
Antidepressant Augmentation: A Review of the Literature and a Review of the Pharmacoeconomic Considerations.
An extremely high dietary iodide supply forestalls severe hypothyroidism in Na+ /I- symporter (NIS) knockout mice
Genomic and Non-Genomic Mechanisms of Action of Thyroid Hormones and Their Catabolite 3,5-Diiodo-L-Thyronine in Mammals.
Biochemical properties of thyroid peroxidase (TPO) expressed in human breast and mammary-derived cell lines
Gestational Hypothyroxinemia Affects Its Offspring With a Reduced Suppressive Capacity Impairing the Outcome of the Experimental Autoimmune Encephalomyelitis
ERGO: Breaking Down the Wall between Human Health and Environmental Testing of Endocrine Disrupters.
Combined effects of di (2-ethylhexyl) phthalate and bisphenol A on thyroid hormone homeostasis in adolescent female rats
Halogen Bonding from the Bonding Perspective with Considerations for Mechanisms of Thyroid Hormone Activation and Inhibition
Visible-Light-Driven Halogen-Bond-Assisted Direct Synthesis of Heteroaryl Thioethers Using Transition-Metal-Free One-Pot C-I Bond Formation/C-S Cross-Coupling Reaction.
Simultaneous enantioselective separation method for thyroid hormones using liquid chromatography-tandem mass spectrometry and its applications.
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