Entry Name Thyroid hormone synthesis
Description Thyroid hormones triiodothyronine (T3) and thyroxine (T4) are essential for normal development, growth and metabolic homeostasis in all vertebrates, and synthesized in the thyroid gland. The functional unit of the thyroid gland is the follicle, delimited by a monolayer of thyrocytes. Polarized thyrocytes surround the follicular lumen; with their basal and apical surfaces facing the bloodstream and the lumen, respectively. To synthesize thyroid hormones, thyrocytes take up iodide at their basal side and concentrate it into the lumen. They also secrete in this lumen the specialized protein thyroglobulin (TG) which serves as a store for the hormones. In the follicular lumen oxidation of iodine, iodination of tyrosines (MIT, 3-monoiodotyrosine; DIT, 3,5-diiodotyrosine) and coupling of iodotyrosines takes place on tyrosine residues in TG, resulting in T3 and T4 synthesis. Iodinated TG is resorbed through the apical membrane and degraded to form T3/T4 in lysosomes; the T3/T4 is then secreted through the basal membrane.
Class Organismal Systems; Endocrine systemBRITE hierarchy
Pathway map Other DBs Orthology K01538 FXYD2, ATP1G1; sodium/potassium-transporting ATPase subunit gamma (FXYD domain-containing ion transport regulator 2)
K01539 ATP1A; sodium/potassium-transporting ATPase subunit alpha [EC:7.2.2.13 ]
K01540 ATP1B, CD298; sodium/potassium-transporting ATPase subunit beta
K04249 TSHR; thyrotropin receptor
K04374 ATF4, CREB2; cyclic AMP-dependent transcription factor ATF-4
K04450 ATF2, CREBP1; cyclic AMP-dependent transcription factor ATF-2
K04632 GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K04634 GNAQ; guanine nucleotide-binding protein G(q) subunit alpha
K04958 ITPR1; inositol 1,4,5-triphosphate receptor type 1
K04959 ITPR2; inositol 1,4,5-triphosphate receptor type 2
K04960 ITPR3; inositol 1,4,5-triphosphate receptor type 3
K05251 TSHB; thyrotropin subunit beta
K05870 CREB1; cyclic AMP-responsive element-binding protein 1
K06233 LRP2; low density lipoprotein-related protein 2
K08522 CGA; glycoprotein hormones alpha chain
K09047 CREB5, CREBPA; cyclic AMP-responsive element-binding protein 5
K09048 CREB3; cyclic AMP-responsive element-binding protein 3
K09049 ATF6B, CREBL1; cyclic AMP-dependent transcription factor ATF-6 beta
K09293 PAX8; paired box protein 8
K09487 HSP90B, TRA1; heat shock protein 90kDa beta
K10063 ASGR1; asialoglycoprotein receptor 1
K10064 ASGR2; asialoglycoprotein receptor 2
K14385 SLC5A5, NIS; solute carrier family 5 (sodium/iodide cotransporter), member 5
K14702 SLC26A4, PDS; solute carrier family 26 (sodium-independent chloride/iodide transporter), member 4
K15173 TTF2; transcription termination factor 2 [EC:5.6.2.-]
K15225 TTF1; transcription termination factor 1
K17232 DUOXA2; dual oxidase maturation factor 2
K20734 SERPINA7, TBG; thyroxine-binding globulin
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
Reference Authors Ahad F, Ganie SA
Title Iodine, Iodine metabolism and Iodine deficiency disorders revisited.
Journal Indian J Endocrinol Metab 14:13-7 (2010)
Reference Authors Gillam MP, Kopp P
Title Genetic defects in thyroid hormone synthesis.
Journal Reference Authors Rokita SE, Adler JM, McTamney PM, Watson JA Jr
Title Efficient use and recycling of the micronutrient iodide in mammals.
Journal Reference Authors Massart C, Hoste C, Virion A, Ruf J, Dumont JE, Van Sande J
Title Cell biology of H2O2 generation in the thyroid: investigation of the control of dual oxidases (DUOX) activity in intact ex vivo thyroid tissue and cell lines.
Journal Reference Authors Bizhanova A, Kopp P
Title Minireview: The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid.
Journal Reference Authors Fong P
Title Thyroid iodide efflux: a team effort?
Journal Reference Authors Song Y, Driessens N, Costa M, De Deken X, Detours V, Corvilain B, Maenhaut C, Miot F, Van Sande J, Many MC, Dumont JE
Title Roles of hydrogen peroxide in thyroid physiology and disease.
Journal Reference Authors Kohn LD, Suzuki K, Nakazato M, Royaux I, Green ED
Title Effects of thyroglobulin and pendrin on iodide flux through the thyrocyte.
Journal Reference Authors Marino M, McCluskey RT
Title Role of thyroglobulin endocytic pathways in the control of thyroid hormone release.
Journal Reference Authors Rivolta CM, Targovnik HM
Title Molecular advances in thyroglobulin disorders.
Journal Reference Authors De La Vieja A, Dohan O, Levy O, Carrasco N
Title Molecular analysis of the sodium/iodide symporter: impact on thyroid and extrathyroid pathophysiology.
Journal Reference Authors Ohye H, Sugawara M
Title Dual oxidase, hydrogen peroxide and thyroid diseases.
Journal Reference Authors Targovnik HM, Esperante SA, Rivolta CM
Title Genetics and phenomics of hypothyroidism and goiter due to thyroglobulin mutations.
Journal Reference Authors Grasberger H
Title Defects of thyroidal hydrogen peroxide generation in congenital hypothyroidism.
Journal Reference Authors Arvan P, Kim PS, Kuliawat R, Prabakaran D, Muresan Z, Yoo SE, Abu Hossain S
Title Intracellular protein transport to the thyrocyte plasma membrane: potential implications for thyroid physiology.
Journal Reference Authors Vono-Toniolo J, Kopp P
Title Thyroglobulin gene mutations and other genetic defects associated with congenital hypothyroidism.
Journal Reference Authors Vitale G, Salvioli S, Franceschi C
Title Oxidative stress and the ageing endocrine system.
Journal Reference Authors Calebiro D, Nikolaev VO, Lohse MJ
Title Imaging of persistent cAMP signaling by internalized G protein-coupled receptors.
Journal Reference Authors Newman CM, Price A, Davies DW, Gray TA, Weetman AP
Title Amiodarone and the thyroid: a practical guide to the management of thyroid dysfunction induced by amiodarone therapy.
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