Thyroid hormones production and their peripheral downstream signalling effects regarding congenital hypothyroidism (Homo sapiens)

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ER4129114111327322910418297353544433114293134113737293229291115730151240329181220203374115381215293210412032214352271422361532152224294617353136193292211623343222731244138295423323222217183732332812332222340113311413111394013243211111112732331, 4742930413118413227323332112029323592927293925, 26434714, 48NucleusFFAProliferative signallingAnterior pituitaryPreoptic areaGrowthDifferentiationTH productionCell proliferationData node for a pathwayEndocytoseLipid dropletBasalmembraneFollicular lumenDownregulationProteolytic cleavageCell differentiationData node for a metaboliteLiverInsulin secretionData node for a gene product which mutation result in CHCell survivalNucleusProduction of DIO1, DIO2 and DIO3AHNEdgesApical membraneARCNodesmTORC1Spontaneous crosslinkingHypothalamusGlutathione metabolismGq stimulationInhibitionAdipose tissuephosphorylationNeuronGs stimulationTo liverCatalyzationNucleusGlucose transportCell cycle arrestSympathetic nervous systemPancreasLegendPVNActivationThyroid follicular cellGlial cellBloodCell growth, proliferationand protein synthesisERConversionLipolysisCold or overfeedingB cell maturationStimulationGs stimulationMAPK signallingNucleusData node for a gene or its productHeat productionin brown ATMEKH2O2cAMPITGBDUOXA2SLC26A4ACTL6BTBG bound T4CASP9Albumin bound T4S6P53SHHHypothalamicAMPKNP-RAdenylate cyclaseTriiodothyronine (T3)PKAAS160SodiumGlycerolJMJD1BtRNAsecFOXO1PRAS40GRB2TTR bound T4T3IP3mTORRASKLBMDM2NorepinephrineTHRB1RHEBGSK3BPOMCTHRmTORPI3KRAPTORInflammationT4TGSOScGMP2O2ZNF516CREBKDM1ADIO1PAX8RAF1Gene productASK1SRCCa2+MetaboliteFRS2NADP+TRHSIRT6TSC1TCA cycleITGATTF1DUOX2MGLLp38TSHMKK3TSC2TSHRPFKFB2AGRPThyroxine (T4)PKCT3NOTCHB-CateninT3RasIYDIP3RCREBBNPPPARGFGF21HypoxiaTTF2SLCO1C1T3BADSECISBP2LANPIodideUCP1MIT and DITT4AQP7DAGPLINRPS6KA6PKGFGFR1AKTMCT8IodideTSC2MLST8RHEBTGTPOMAFARXRNPYNADPH PIP3SLC16A10TREATGLPathwayOxidative phosphorylationATF2PCG-1T3ACERKNOTCH signallingTG bound MIT, DIT, T3 and T4NHSLSLC5A5Beta-3 ARmTORWntDownregulatedWnt signallingPRDM16FFAMC4RRPS6KB1IodidePLCTG bound MIT and DITTG bound MIT, DIT, T3 and T4TBG bound T3Albumin bound T3TTR bound T3MCT8cAMPPKAphosphorylationDGMG35353FGF213phosphorylation3phosphorylationphosphorylationUCP122MCT829MCT8DIO2T4T3DIO2MCT8MCT8T3T2SHHDIO3NucleusT3SLC16A1040ITGBITGA343434T3THRA1132252616Glucose metabolismDAGPKCIP3IP3RCa2+PLC1111111111cAMP11PKA11, 45TRETHRRXRNucleusT3MCT8T4MCT8T4T3DIO2SodiumTRERXRT3THRB1IodideGene product


Congenital hypothyroidism is a hormonal disorder of the thyroid hormone production which results in increased birth weight, impaired glucose metabolism and decreased body temperature. Above, an overview of thyroid hormones production occurring in thyroid gland and their relevant downstream signalling for congenital hypothyroidism is displayed. As the legend states, known prevalent gene mutations that lead to congenital hypothyroidism are colored red.

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  1. Contreras C, Nogueiras R, Diéguez C, Rahmouni K, López M; ''Traveling from the hypothalamus to the adipose tissue: The thermogenic pathway.''; Redox Biol, 2017 PubMed Europe PMC
  2. Houddane A, Bultot L, Novellasdemunt L, Johanns M, Gueuning MA, Vertommen D, Coulie PG, Bartrons R, Hue L, Rider MH; ''Role of Akt/PKB and PFKFB isoenzymes in the control of glycolysis, cell proliferation and protein synthesis in mitogen-stimulated thymocytes.''; Cell Signal, 2017 PubMed Europe PMC
  3. Minard AY, Tan SX, Yang P, Fazakerley DJ, Domanova W, Parker BL, Humphrey SJ, Jothi R, Stöckli J, James DE; ''mTORC1 Is a Major Regulatory Node in the FGF21 Signaling Network in Adipocytes.''; Cell Rep, 2016 PubMed Europe PMC
  4. Song Y, Driessens N, Costa M, De Deken X, Detours V, Corvilain B, Maenhaut C, Miot F, Van Sande J, Many MC, Dumont JE; ''Roles of hydrogen peroxide in thyroid physiology and disease.''; J Clin Endocrinol Metab, 2007 PubMed Europe PMC
  5. Schakman O, Kalista S, Bertrand L, Lause P, Verniers J, Ketelslegers JM, Thissen JP; ''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.''; Endocrinology, 2008 PubMed Europe PMC
  6. Yao L, Cui X, Chen Q, Yang X, Fang F, Zhang J, Liu G, Jin W, Chang Y; ''''; , PubMed Europe PMC
  7. Fenzl A, Kiefer FW; ''Brown adipose tissue and thermogenesis.''; Horm Mol Biol Clin Investig, 2014 PubMed Europe PMC
  8. Mao LM, Tang Q, Wang JQ; ''Protein kinase C-regulated cAMP response element-binding protein phosphorylation in cultured rat striatal neurons.''; Brain Res Bull, 2007 PubMed Europe PMC
  9. Lebeck J; ''Metabolic impact of the glycerol channelsAQP7 and AQP9 in adipose tissue and liver.''; J Mol Endocrinol, 2014 PubMed Europe PMC
  10. Dentice M, Luongo C, Huang S, Ambrosio R, Elefante A, Mirebeau-Prunier D, Zavacki AM, Fenzi G, Grachtchouk M, Hutchin M, Dlugosz AA, Bianco AC, Missero C, Larsen PR, Salvatore D; ''Sonic hedgehog-induced type 3 deiodinase blocks thyroid hormone action enhancing proliferation of normal and malignant keratinocytes.''; Proc Natl Acad Sci U S A, 2007 PubMed Europe PMC
  11. Davis PJ, Davis FB, Lin HY; ''Promotion by thyroid hormone of cytoplasm-to-nucleus shuttling of thyroid hormone receptors.''; Steroids, 2008 PubMed Europe PMC
  12. Zois NE, Bartels ED, Hunter I, Kousholt BS, Olsen LH, Goetze JP; ''Natriuretic peptides in cardiometabolic regulation and disease.''; Nat Rev Cardiol, 2014 PubMed Europe PMC
  13. Mîinea CP, Sano H, Kane S, Sano E, Fukuda M, Peränen J, Lane WS, Lienhard GE; ''AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain.''; Biochem J, 2005 PubMed Europe PMC
  14. Huang H, Shi Y, Liang B, Cai H, Cai Q; ''Iodinated TG in Thyroid Follicular Lumen Regulates TTF-1 and PAX8 Expression via TSH/TSHR Signaling Pathway.''; J Cell Biochem, 2017 PubMed Europe PMC
  15. Calebiro D, Nikolaev VO, Lohse MJ; ''Imaging of persistent cAMP signaling byinternalized G protein-coupled receptors.''; J Mol Endocrinol, 2010 PubMed Europe PMC
  16. Chen J, Bell J, Lau BT, Whittaker T, Stapleton D, Ji HP; ''A functional CRISPR/Cas9 screen identifies kinases that modulate FGFR inhibitor response in gastric cancer.''; Oncogenesis, 2019 PubMed Europe PMC
  17. Spirli C, Morell CM, Locatelli L, Okolicsanyi S, Ferrero C, Kim AK, Fabris L, Fiorotto R, Strazzabosco M; ''Cyclic AMP/PKA-dependent paradoxical activation of Raf/MEK/ERK signaling in polycystin-2 defective mice treatedwith sorafenib.''; Hepatology, 2012 PubMed Europe PMC
  18. Cvoro A, Devito L, Milton FA, Noli L, Zhang A, Filippi C, Sakai K, Suh JH, H Sieglaff D, Dhawan A, Sakai T, Ilic D, Webb P; ''A thyroid hormone receptor/KLF9 axis in human hepatocytes and pluripotent stem cells.''; Stem Cells, 2015 PubMed Europe PMC
  19. Cheng AW, Bolognesi M, Kraus VB; ''DIO2 modifies inflammatory responses in chondrocytes.''; Osteoarthritis Cartilage, 2012 PubMed Europe PMC
  20. Bizhanova A, Kopp P; ''Minireview: The sodium-iodide symporter NIS and pendrin in iodide homeostasis of the thyroid.''; Endocrinology, 2009 PubMed Europe PMC
  21. Massart C, Hoste C, Virion A, Ruf J, Dumont JE, Van Sande J; ''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.''; Mol Cell Endocrinol, 2011 PubMed Europe PMC
  22. Frühbeck G, Méndez-Giménez L, Fernández-Formoso JA, Fernández S, Rodríguez A; ''Regulation of adipocyte lipolysis.''; Nutr Res Rev, 2014 PubMed Europe PMC
  23. Dumitrescu AM, Refetoff S; ''Inherited defects of thyroid hormone metabolism.''; Ann Endocrinol (Paris), 2011 PubMed Europe PMC
  24. Hondares E, Iglesias R, Giralt A, Gonzalez FJ, Giralt M, Mampel T, Villarroya F; ''Thermogenic activation induces FGF21 expression and release in brown adipose tissue.''; J Biol Chem, 2011 PubMed Europe PMC
  25. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME; ''Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery.''; Cell, 1997 PubMed Europe PMC
  26. Zhang X, Tang N, Hadden TJ, Rishi AK; ''Akt, FoxO and regulation of apoptosis.''; Biochim Biophys Acta, 2011 PubMed Europe PMC
  27. Inoki K, Li Y, Zhu T, Wu J, Guan KL; ''TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling.''; Nat Cell Biol, 2002 PubMed Europe PMC
  28. Rivolta CM, Targovnik HM; ''Molecular advances in thyroglobulin disorders.''; Clin Chim Acta, 2006 PubMed Europe PMC
  29. Kouidhi S, Clerget-Froidevaux MS; ''Integrating Thyroid Hormone Signaling in Hypothalamic Control of Metabolism: Crosstalk Between Nuclear Receptors.''; Int J Mol Sci, 2018 PubMed Europe PMC
  30. Ahad F, Ganie SA; ''''; , PubMed Europe PMC
  31. Miller LD, Park KS, Guo QM, Alkharouf NW, Malek RL, Lee NH, Liu ET, Cheng SY; ''Silencing of Wnt signaling and activation of multiple metabolic pathways in response to thyroid hormone-stimulated cell proliferation.''; Mol Cell Biol, 2001 PubMed Europe PMC
  32. Schwartz CE, Stevenson RE; ''''; , PubMed Europe PMC
  33. Robidoux J, Cao W, Quan H, Daniel KW, Moukdar F, Bai X, Floering LM, Collins S; ''Selective activation of mitogen-activated protein (MAP) kinase kinase 3 and p38alpha MAP kinase is essential for cyclic AMP-dependent UCP1 expression in adipocytes.''; Mol Cell Biol, 2005 PubMed Europe PMC
  34. Cheng SY, Leonard JL, Davis PJ; ''Molecular aspects of thyroid hormone actions.''; Endocr Rev, 2010 PubMed Europe PMC
  35. Villarroya F, Peyrou M, Giralt M; ''Transcriptional regulation of the uncoupling protein-1 gene.''; Biochimie, 2017 PubMed Europe PMC
  36. López M, Varela L, Vázquez MJ, Rodríguez-Cuenca S, González CR, Velagapudi VR, Morgan DA, Schoenmakers E, Agassandian K, Lage R, Martínez de Morentin PB, Tovar S, Nogueiras R, Carling D, Lelliott C, Gallego R, Oresic M, Chatterjee K, Saha AK, Rahmouni K, Diéguez C, Vidal-Puig A; ''Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance.''; Nat Med, 2010 PubMed Europe PMC
  37. Gałecka E, Talarowska M, Maes M, Su KP, Górski P, Szemraj J; ''Polymorphisms of iodothyronine deiodinases (DIO1, DIO3) genes are not associated with recurrent depressive disorder.''; Pharmacol Rep, 2016 PubMed Europe PMC
  38. Bartalena L, Robbins J; ''Thyroid hormone transport proteins.''; Clin Lab Med, 1993 PubMed Europe PMC
  39. Simonides WS, Mulcahey MA, Redout EM, Muller A, Zuidwijk MJ, Visser TJ, Wassen FW, Crescenzi A, da-Silva WS, Harney J, Engel FB, Obregon MJ, Larsen PR, Bianco AC, Huang SA; ''Hypoxia-inducible factor induces local thyroid hormone inactivation during hypoxic-ischemic disease in rats.''; J Clin Invest, 2008 PubMed Europe PMC
  40. Mariotta L, Ramadan T, Singer D, Guetg A, Herzog B, Stoeger C, Palacín M, Lahoutte T, Camargo SM, Verrey F; ''T-type amino acid transporter TAT1 (Slc16a10) is essential for extracellular aromatic amino acid homeostasis control.''; J Physiol, 2012 PubMed Europe PMC
  41. Rokita SE, Adler JM, McTamney PM, Watson JA Jr; ''Efficient use and recycling of the micronutrient iodide in mammals.''; Biochimie, 2010 PubMed Europe PMC
  42. Fernandez-Marcos PJ, Nóbrega-Pereira S; ''NADPH: new oxygen for the ROS theory of aging.''; Oncotarget, 2016 PubMed Europe PMC
  43. Aguayo-Mazzucato C, DiIenno A, Hollister-Lock J, Cahill C, Sharma A, Weir G, Colton C, Bonner-Weir S; ''MAFA and T3 Drive Maturation of Both Fetal Human Islets and Insulin-Producing Cells Differentiated From hESC.''; J Clin Endocrinol Metab, 2015 PubMed Europe PMC
  44. Song H, Smolen P, Av-Ron E, Baxter DA, Byrne JH; ''Bifurcation and singularity analysis of a molecular network for the induction of long-term memory.''; Biophys J, 2006 PubMed Europe PMC
  45. Oetting A, Yen PM; ''New insights into thyroid hormone action.''; Best Pract Res Clin Endocrinol Metab, 2007 PubMed Europe PMC
  46. Feliciello A, Allevato G, Musti AM, De Brasi D, Gallo A, Avvedimento VE, Gottesman ME; ''Thyroid transcription factor 1 phosphorylation is not required for protein kinase A-dependent transcription of the thyroglobulin promoter.''; Cell Growth Differ, 2000 PubMed Europe PMC
  47. Kooijman S, van den Heuvel JK, Rensen PCN; ''Neuronal Control of Brown Fat Activity.''; Trends Endocrinol Metab, 2015 PubMed Europe PMC
  48. Mao LM, Tang Q, Wang JQ; ''''; , PubMed Europe PMC


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108263view14:56, 3 December 2019L DupuisConverted interactions to graphical lines in legend
108262view14:55, 3 December 2019L DupuisConnected unconnected lines
108096view12:55, 28 November 2019FehrhartOntology Term : 'congenital hypothyroidism' added !
108095view12:52, 28 November 2019FehrhartOntology Term : 'disease pathway' added !
107964view09:26, 18 November 2019FehrhartOntology Term : 'thyroid-stimulating hormone signaling pathway' added !
107960view09:14, 14 November 2019Rik-lahaijeModified description
107959view09:09, 14 November 2019Rik-lahaijeModified title
107958view09:09, 14 November 2019Rik-lahaijeNew pathway

External references


View all...
NameTypeDatabase referenceComment
ACProteinA0A0K0K1K3 (Uniprot-TrEMBL)
ACTL6BGeneProductENSG00000077080 (Ensembl)
AGRPGeneProductENSG00000159723 (Ensembl)
AKTGeneProductENSG00000117020 (Ensembl)
ANPProteinA0A087X094 (Uniprot-TrEMBL)
AQP7GeneProductENSG00000165269 (Ensembl)
AS160GeneProductENSG00000136111 (Ensembl)
ASK1ProteinG3V4Q4 (Uniprot-TrEMBL)
ATF2GeneProductENSG00000115966 (Ensembl)
ATGLProteinQ96AD5 (Uniprot-TrEMBL)
Adenylate cyclaseProteinA0A0A0MSC1 (Uniprot-TrEMBL)
Albumin bound T3Complex
Albumin bound T4Complex
B-Catenin GeneProductENSG00000168036 (Ensembl)
BADGeneProductENSG00000002330 (Ensembl)
BNPProteinP16860 (Uniprot-TrEMBL)
Beta-3 ARProteinP13945 (Uniprot-TrEMBL)
CASP9GeneProductENSG00000132906 (Ensembl)
CREB GeneProductENSG00000107175 (Ensembl)
Ca2+Metabolite29108 (ChEBI)
DIO1GeneProductENSG00000211452 (Ensembl)
DIO2GeneProductENSG00000211448 (Ensembl)
DIO3GeneProductENSG00000197406 (Ensembl)
DUOX2GeneProductENSG00000140279 (Ensembl)
DUOXA2GeneProductENSG00000140274 (Ensembl)
Downregulated Wnt signallingPathwaymap04310 (KEGG Pathway)
ERKProteinP28482 (Uniprot-TrEMBL)
FGF21GeneProductENSG00000105550 (Ensembl)
FGFR1GeneProductENSG00000077782 (Ensembl)
FOXO1GeneProductENSG00000150907 (Ensembl)
FRS2GeneProductENSG00000166225 (Ensembl)
GRB2GeneProductENSG00000177885 (Ensembl)
GSK3BGeneProductENSG00000082701 (Ensembl)
Gene productGeneProduct
Hypothalamic AMPKMetabolite
IP3RGeneProductENSG00000123104 (Ensembl)
ITGAGeneProductENSG00000138448 (Ensembl)
ITGBGeneProductENSG00000259207 (Ensembl)
IYDGeneProductENSG00000009765 (Ensembl)
InflammationPathwayWP453 (WikiPathways)
IodideMetaboliteQ27259563 (Wikidata)
JMJD1BProteinQ7LBC6 (Uniprot-TrEMBL)
KDM1AGeneProductENSG00000004487 (Ensembl)
KLBGeneProductENSG00000134962 (Ensembl)
MAFAGeneProductENSG00000182759 (Ensembl)
MC4RGeneProductENSG00000166603 (Ensembl)
MCT8ProteinP36021 (Uniprot-TrEMBL)
MDM2GeneProductENSG00000135679 (Ensembl)
MEKProteinQ02750 (Uniprot-TrEMBL)
MGLLGeneProductENSG00000074416 (Ensembl)
MIT and DITMetabolite
MKK3 ProteinA0A024R2W7 (Uniprot-TrEMBL)
MLST8GeneProductENSG00000167965 (Ensembl)
NADPH Metabolite
NHSLGeneProductENSG00000135540 (Ensembl)
NOTCH signallingPathwaymap04330 (KEGG Pathway)
NOTCHGeneProductENSG00000148400 (Ensembl)
NP-RProteinP16066 (Uniprot-TrEMBL)
NPYGeneProductENSG00000122585 (Ensembl)
Oxidative phosphorylationPathwaymap00190 (KEGG Pathway)
P53GeneProductENSG00000141510 (Ensembl)
PAX8ProteinA0A140TA56 (Uniprot-TrEMBL)
PCG-1 GeneProductENSG00000109819 (Ensembl)
PFKFB2GeneProductENSG00000123836 (Ensembl)
PI3KGeneProductENSG00000121879 (Ensembl)
PKAProteinQ15136 (Uniprot-TrEMBL)
PKCProteinA0A087X0I9 (Uniprot-TrEMBL)
PLCProteinA0A087WT80 (Uniprot-TrEMBL)
PLINGeneProductENSG00000166819 (Ensembl)
POMCGeneProductENSG00000115138 (Ensembl)
PPARGGeneProductENSG00000132170 (Ensembl)
PRAS40GeneProductENSG00000204673 (Ensembl)
PRDM16GeneProductENSG00000142611 (Ensembl)
RAF1GeneProductENSG00000132155 (Ensembl)
RAPTORGeneProductENSG00000141564 (Ensembl)
RASGeneProductENSG00000174775 (Ensembl)
RHEBGeneProductENSG00000106615 (Ensembl)
RPS6KA6GeneProductENSG00000072133 (Ensembl)
RPS6KB1GeneProductENSG00000108443 (Ensembl)
RXRGeneProductENSG00000186350 (Ensembl)
RasGeneProductENSG00000174775 (Ensembl)
S6GeneProductENSG00000137154 (Ensembl)
SECISBP2LGeneProductENSG00000138593 (Ensembl)
SHHGeneProductENSG00000164690 (Ensembl)
SIRT6GeneProductENSG00000077463 (Ensembl)
SLC16A10GeneProductENSG00000112394 (Ensembl)
SLC26A4GeneProductENSG00000091137 (Ensembl)
SLC5A5GeneProductENSG00000105641 (Ensembl)
SLCO1C1GeneProductENSG00000139155 (Ensembl)
SOSGeneProductENSG00000115904 (Ensembl)
SRCGeneProductENSG00000197122 (Ensembl)
T4 Metabolite
TBG bound T3GeneProduct
TBG bound T4GeneProduct
TCA cycle Pathwaymap00020 (KEGG Pathway)
TG bound MIT and DITComplexE5RG33 (Uniprot-TrEMBL)
TG bound MIT, DIT, T3 and T4ComplexE5RG33 (Uniprot-TrEMBL)
TGProteinE5RG33 (Uniprot-TrEMBL)
THRA1GeneProductENSG00000126351 (Ensembl)
THRB1GeneProductENSG00000151090 (Ensembl)
THRProteinP10827 (Uniprot-TrEMBL)
TPOProteinE9PFM6 (Uniprot-TrEMBL)
TRHGeneProductENSG00000170893 (Ensembl)
TSC1GeneProductENSG00000165699 (Ensembl)
TSC2GeneProductENSG00000103197 (Ensembl)
TSHGeneProductENSG00000134200 (Ensembl)
TSHRGeneProductENSG00000165409 (Ensembl)
TTF1GeneProductENSG00000125482 (Ensembl)
TTF2GeneProductENSG00000116830 (Ensembl)
TTR bound T3 Complex
TTR bound T4Complex
Thyroxine (T4)Metabolite
Triiodothyronine (T3)Metabolite
UCP1GeneProductENSG00000109424 (Ensembl)
WntGeneProductENSG00000162552 (Ensembl)
ZNF516GeneProductENSG00000101493 (Ensembl)
mTORGeneProductENSG00000198793 (Ensembl)
mTORPathwaymap04150 (KEGG Pathway)
p38ProteinQ16539 (Uniprot-TrEMBL)

Annotated Interactions

No annotated interactions

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