Thyroid hormones production and peripheral downstream signaling effects (WP4746)
Homo sapiens
Congenital hypothyroidism is a genetic hormonal disorder regarding the thyroid hormone. Due dyshormonogenesis, the production of the thyroid hormones is impaired resulting in increased birth weight, reduced LDL breakdown, decreased lipolysis, impaired glucose metabolism and decreased body temperature. Above, an overview of thyroid hormones production occurring in thyroid gland and their relevant downstream signalling is displayed. As the legend states, genes known te be affected by mutations leading to congenital hypothyroidism are colored red.
Authors
Rik Lahaije , Friederike Ehrhart , Lauren J. Dupuis , Marvin Martens , Egon Willighagen , and Eric WeitzActivity
Discuss this pathway
Check for ongoing discussions or start your own.
Cited In
Are you planning to include this pathway in your next publication? See How to Cite and add a link here to your paper once it's online.
Organisms
Homo sapiensCommunities
Diseases Rare DiseasesAnnotations
Cell Type Ontology
glial cell neuron thyroid follicular cellDisease Ontology
congenital hypothyroidismPathway Ontology
thyroid-stimulating hormone signaling pathway disease pathwayReferences
- Thyroid hormone transport proteins. Bartalena L, Robbins J. Clin Lab Med. 1993 Sep;13(3):583–98. PubMed Europe PMC Scholia
- Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, et al. Cell. 1997 Oct 17;91(2):231–41. PubMed Europe PMC Scholia
- Thyroid transcription factor 1 phosphorylation is not required for protein kinase A-dependent transcription of the thyroglobulin promoter. Feliciello A, Allevato G, Musti AM, De Brasi D, Gallo A, Avvedimento VE, et al. Cell Growth Differ. 2000 Dec;11(12):649–54. PubMed Europe PMC Scholia
- Silencing of Wnt signaling and activation of multiple metabolic pathways in response to thyroid hormone-stimulated cell proliferation. Miller LD, Park KS, Guo QM, Alkharouf NW, Malek RL, Lee NH, et al. Mol Cell Biol. 2001 Oct;21(19):6626–39. PubMed Europe PMC Scholia
- TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Inoki K, Li Y, Zhu T, Wu J, Guan KL. Nat Cell Biol. 2002 Sep;4(9):648–57. PubMed Europe PMC Scholia
- Selective activation of mitogen-activated protein (MAP) kinase kinase 3 and p38alpha MAP kinase is essential for cyclic AMP-dependent UCP1 expression in adipocytes. Robidoux J, Cao W, Quan H, Daniel KW, Moukdar F, Bai X, et al. Mol Cell Biol. 2005 Jul;25(13):5466–79. PubMed Europe PMC Scholia
- AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain. Mîinea CP, Sano H, Kane S, Sano E, Fukuda M, Peränen J, et al. Biochem J. 2005 Oct 1;391(Pt 1):87–93. PubMed Europe PMC Scholia
- Bifurcation and singularity analysis of a molecular network for the induction of long-term memory. Song H, Smolen P, Av-Ron E, Baxter DA, Byrne JH. Biophys J. 2006 Apr 1;90(7):2309–25. PubMed Europe PMC Scholia
- Molecular advances in thyroglobulin disorders. Rivolta CM, Targovnik HM. Clin Chim Acta. 2006 Dec;374(1–2):8–24. PubMed Europe PMC Scholia
- Protein kinase C-regulated cAMP response element-binding protein phosphorylation in cultured rat striatal neurons. Mao LM, Tang Q, Wang JQ. Brain Res Bull. 2007 May 30;72(4–6):302–8. PubMed Europe PMC Scholia
- New insights into thyroid hormone action. Oetting A, Yen PM. Best Pract Res Clin Endocrinol Metab. 2007 Jun;21(2):193–208. PubMed Europe PMC Scholia
- The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome. Schwartz CE, Stevenson RE. Best Pract Res Clin Endocrinol Metab. 2007 Jun;21(2):307–21. PubMed Europe PMC Scholia
- Roles of hydrogen peroxide in thyroid physiology and disease. Song Y, Driessens N, Costa M, De Deken X, Detours V, Corvilain B, et al. J Clin Endocrinol Metab. 2007 Oct;92(10):3764–73. PubMed Europe PMC Scholia
- Sonic hedgehog-induced type 3 deiodinase blocks thyroid hormone action enhancing proliferation of normal and malignant keratinocytes. Dentice M, Luongo C, Huang S, Ambrosio R, Elefante A, Mirebeau-Prunier D, et al. Proc Natl Acad Sci U S A. 2007 Sep 4;104(36):14466–71. PubMed Europe PMC Scholia
- Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats. Simonides WS, Mulcahey MA, Redout EM, Muller A, Zuidwijk MJ, Visser TJ, et al. J Clin Invest. 2008 Mar;118(3):975–83. PubMed Europe PMC Scholia
- Promotion by thyroid hormone of cytoplasm-to-nucleus shuttling of thyroid hormone receptors. Davis PJ, Davis FB, Lin HY. Steroids. 2008 Oct;73(9–10):1013–7. PubMed Europe PMC Scholia
- Role of Akt/GSK-3beta/beta-catenin transduction pathway in the muscle anti-atrophy action of insulin-like growth factor-I in glucocorticoid-treated rats. Schakman O, Kalista S, Bertrand L, Lause P, Verniers J, Ketelslegers JM, et al. Endocrinology. 2008 Aug;149(8):3900–8. PubMed Europe PMC Scholia
- Minireview: The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid. Bizhanova A, Kopp P. Endocrinology. 2009 Mar;150(3):1084–90. PubMed Europe PMC Scholia
- Molecular aspects of thyroid hormone actions. Cheng SY, Leonard JL, Davis PJ. Endocr Rev. 2010 Apr;31(2):139–70. PubMed Europe PMC Scholia
- Efficient use and recycling of the micronutrient iodide in mammals. Rokita SE, Adler JM, McTamney PM, Watson JA Jr. Biochimie. 2010 Sep;92(9):1227–35. PubMed Europe PMC Scholia
- Imaging of persistent cAMP signaling by internalized G protein-coupled receptors. Calebiro D, Nikolaev VO, Lohse MJ. J Mol Endocrinol. 2010 Jul;45(1):1–8. PubMed Europe PMC Scholia
- Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. López M, Varela L, Vázquez MJ, Rodríguez-Cuenca S, González CR, Velagapudi VR, et al. Nat Med. 2010 Sep;16(9):1001–8. PubMed Europe PMC Scholia
- Thermogenic activation induces FGF21 expression and release in brown adipose tissue. Hondares E, Iglesias R, Giralt A, Gonzalez FJ, Giralt M, Mampel T, et al. J Biol Chem. 2011 Apr 15;286(15):12983–90. PubMed Europe PMC Scholia
- Akt, FoxO and regulation of apoptosis. Zhang X, Tang N, Hadden TJ, Rishi AK. Biochim Biophys Acta. 2011 Nov;1813(11):1978–86. PubMed Europe PMC Scholia
- Iodine, Iodine metabolism and Iodine deficiency disorders revisited. Ahad F, Ganie SA. Indian J Endocrinol Metab. 2010 Jan;14(1):13–7. PubMed Europe PMC Scholia
- Inherited defects of thyroid hormone metabolism. Dumitrescu AM, Refetoff S. Ann Endocrinol (Paris). 2011 Apr;72(2):95–8. PubMed Europe PMC Scholia
- 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. Massart C, Hoste C, Virion A, Ruf J, Dumont JE, Van Sande J. Mol Cell Endocrinol. 2011 Aug 22;343(1–2):32–44. PubMed Europe PMC Scholia
- DIO2 modifies inflammatory responses in chondrocytes. Cheng AWM, Bolognesi M, Kraus VB. Osteoarthritis Cartilage. 2012 May;20(5):440–5. PubMed Europe PMC Scholia
- Cyclic AMP/PKA-dependent paradoxical activation of Raf/MEK/ERK signaling in polycystin-2 defective mice treated with sorafenib. Spirli C, Morell CM, Locatelli L, Okolicsanyi S, Ferrero C, Kim AK, et al. Hepatology. 2012 Dec;56(6):2363–74. PubMed Europe PMC Scholia
- T-type amino acid transporter TAT1 (Slc16a10) is essential for extracellular aromatic amino acid homeostasis control. Mariotta L, Ramadan T, Singer D, Guetg A, Herzog B, Stoeger C, et al. J Physiol. 2012 Dec 15;590(24):6413–24. PubMed Europe PMC Scholia
- Metabolic impact of the glycerol channels AQP7 and AQP9 in adipose tissue and liver. Lebeck J. J Mol Endocrinol. 2014 Mar 14;52(2):R165-78. PubMed Europe PMC Scholia
- Natriuretic peptides in cardiometabolic regulation and disease. Zois NE, Bartels ED, Hunter I, Kousholt BS, Olsen LH, Goetze JP. Nat Rev Cardiol. 2014 Jul;11(7):403–12. PubMed Europe PMC Scholia
- Regulation of adipocyte lipolysis. Frühbeck G, Méndez-Giménez L, Fernández-Formoso JA, Fernández S, Rodríguez A. Nutr Res Rev. 2014 Jun;27(1):63–93. PubMed Europe PMC Scholia
- A thyroid hormone receptor/KLF9 axis in human hepatocytes and pluripotent stem cells. Cvoro A, Devito L, Milton FA, Noli L, Zhang A, Filippi C, et al. Stem Cells. 2015 Feb;33(2):416–28. PubMed Europe PMC Scholia
- Brown adipose tissue and thermogenesis. Fenzl A, Kiefer FW. Horm Mol Biol Clin Investig. 2014 Jul;19(1):25–37. PubMed Europe PMC Scholia
- MAFA and T3 Drive Maturation of Both Fetal Human Islets and Insulin-Producing Cells Differentiated From hESC. Aguayo-Mazzucato C, DiIenno A, Hollister-Lock J, Cahill C, Sharma A, Weir G, et al. J Clin Endocrinol Metab. 2015 Oct;100(10):3651–9. PubMed Europe PMC Scholia
- Neuronal Control of Brown Fat Activity. Kooijman S, van den Heuvel JK, Rensen PCN. Trends Endocrinol Metab. 2015 Nov;26(11):657–68. PubMed Europe PMC Scholia
- Polymorphisms of iodothyronine deiodinases (DIO1, DIO3) genes are not associated with recurrent depressive disorder. Gałecka E, Talarowska M, Maes M, Su KP, Górski P, Szemraj J. Pharmacol Rep. 2016 Oct;68(5):913–7. PubMed Europe PMC Scholia
- NADPH: new oxygen for the ROS theory of aging. Fernandez-Marcos PJ, Nóbrega-Pereira S. Oncotarget. 2016 Aug 9;7(32):50814–5. PubMed Europe PMC Scholia
- mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes. Minard AY, Tan SX, Yang P, Fazakerley DJ, Domanova W, Parker BL, et al. Cell Rep. 2016 Sep 27;17(1):29–36. PubMed Europe PMC Scholia
- Transcriptional regulation of the uncoupling protein-1 gene. Villarroya F, Peyrou M, Giralt M. Biochimie. 2017 Mar;134:86–92. PubMed Europe PMC Scholia
- Role of Akt/PKB and PFKFB isoenzymes in the control of glycolysis, cell proliferation and protein synthesis in mitogen-stimulated thymocytes. Houddane A, Bultot L, Novellasdemunt L, Johanns M, Gueuning MA, Vertommen D, et al. Cell Signal. 2017 Jun;34:23–37. PubMed Europe PMC Scholia
- Iodinated TG in Thyroid Follicular Lumen Regulates TTF-1 and PAX8 Expression via TSH/TSHR Signaling Pathway. Huang H, Shi Y, Liang B, Cai H, Cai Q. J Cell Biochem. 2017 Oct;118(10):3444–51. PubMed Europe PMC Scholia
- Traveling from the hypothalamus to the adipose tissue: The thermogenic pathway. Contreras C, Nogueiras R, Diéguez C, Rahmouni K, López M. Redox Biol. 2017 Aug;12:854–63. PubMed Europe PMC Scholia
- Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat. Yao L, Cui X, Chen Q, Yang X, Fang F, Zhang J, et al. Cell Rep. 2017 Jul 18;20(3):641–54. PubMed Europe PMC Scholia
- Integrating Thyroid Hormone Signaling in Hypothalamic Control of Metabolism: Crosstalk Between Nuclear Receptors. Kouidhi S, Clerget-Froidevaux MS. Int J Mol Sci. 2018 Jul 11;19(7):2017. PubMed Europe PMC Scholia
- A functional CRISPR/Cas9 screen identifies kinases that modulate FGFR inhibitor response in gastric cancer. Chen J, Bell J, Lau BT, Whittaker T, Stapleton D, Ji HP. Oncogenesis. 2019 May 10;8(5):33. PubMed Europe PMC Scholia