Historic Background
Historically, the monoamine serotonin (5-hydroxytryptamine, 5-HT) was first discovered in the gastrointestinal (GI) tract as a contractile substance, enteramine. Subsequently, 5-HT was discovered in blood (serum) as a potent vasoconstrictive substance (enteramine was shown to be the same substance as 5-HT), in the central nervous system (CNS) as a neurotransmitter, and in the pineal gland as an intermediate precursor in the synthesis of melatonin, the neurohormone involving in the regulation of the circadian rhythm (Amireault et al. 2013).
About 95% of the body’s 5-HT resides in the GI tract, primarily (90%) in a subtype of enteroendocrine cells distributed throughout in the GI tract called enterochromaffin (EC) cells and 10% in serotonergic neurons of myenteric plexus. 5-HT originating from the GI tract acts locally or is released in the blood stream and...
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Altarejos JY, Montminy M. CREB and the CRTC co-activators: sensors for hormonal and metabolic signals. Nat Rev Mol Cell Biol. 2011;12:141–51. https://doi.org/10.1038/nrm3072.
Amireault P, Sibon D, Côté F. Life without peripheral serotonin: insights from tryptophan hydroxylase 1 knockout mice reveal the exsistence of paracrine/autocrine serotonergic networks. ACS Chem Neurosci. 2013;4:64–71. https://doi.org/10.1021/cn300154j.
Ballas N, Mandel G. The many faces of REST oversee epigenetic programming of neuronal genes. Curr Opin Neurobiol. 2005;15:500–6.
Bockaert J, Claeysen S, Dumuis A, Martin P. Classification and signaling characteristics of 5-HT receptors. In: Muller CP, Jacobs BL, editors. Handbook of behavioral neurobiology of serotonin. San Diego: Academic Press; 2010. p. 103–21.
Chen GL, Miller GM. Advances in tryptophan hydroxylase-2 gene expression regulation: new insights into serotonin-stress interaction and clinical implications. Am J Med Genet Part B. 2013;159B:152–71. https://doi.org/10.1002/ajmg.b.32023.
Chen GL, Vallender EJ, Miller GM. Functional characterization of the TPH2 5′ regulatory region: untranslated region and polymorphisms modulate gene expression in vitro. Hum Genet. 2008;122:645–57. https://doi.org/10.1007/s00439-007-0443-y.
Gentile MT, Nawa Y, Lunardi G, Florio T, Matsui H, Colucci-D’Amato L. Tryptophan hydroxylase 2 (TPH2) in a neuronal cell line: modulation by cell differentiation and NRSF/rest activity. J Neurochem. 2012;123:963–70. https://doi.org/10.1111/jnc.12004.
Goswami DB, May WL, Stockmeier CA, Austin MC. Transcriptional expression of serotonergic regulators in laser-captured microdissected dorsal raphe neurons of subjects with major depressive disorder: sex-specific differences. J Neurochem. 2010;112:397–409. doi:10.1111/j.1471- 4159.2009. 06462.x.
Hasegawa H, Nakamura K. Tryptophan hydroxylase and serotonin synthesis regulation. In: Muller CP, Jacobs BL, editors. Handbook of behavioral neurobiology of serotonin. San Diego: Academic Press; 2010. p. 183–202.
Hiroi R, Handa RJ. Estrogen receptor-β regulates human tryptophan hydroxylase-2 through an estrogen response element in the 5′ untranslated region. J Neurochem. 2013;127:487–95. https://doi.org/10.1111/jnc.12401.
Jacobsen JPR, Medvedev IO, Carom MG. The 5-HT deficiency theory of depression: perspectives from a naturalistic 5-HT deficiency model, the tryptophan hydroxylase 2 Arg439His knockin mouse. Philos Trans R Soc B. 2012;367:2449–59. https://doi.org/10.1098/rstb.2012.0109.
Lenicov FR, Lemonde S, Czesak M, Mosher TM, Albert PR. Cell-type specific induction of tryptophan hydroxylase-2 transcription by calcium mobilization. J Neurochem. 2007;103:2047–57. https://doi.org/10.1111/j.1471-4159.2007.04903.x.
McKinney JA, Turel B, Winge I, Knappskog PM, Haavik J. Functional properties of missense variants of human tryptophan hydroxylase 2. Hum Mutat. 2009;30:787–94. https://doi.org/10.1002/humu.20956.
Nasu M, Yada S, Igarashi A, Sutoo D, Akiyama K, Ito M, Yoshida N, Ueda S. Mammalian-specific sequences in pou3f2 contribute to maternal behavior. Genome Biol Evol. 2014;6:1145–56. https://doi.org/10.1093/gbe/evu072.
Ooi L, Wood IC. Chromatin crosstalk in development and disease: lessons from REST. Hum Mutat. 2009;30:787–94. https://doi.org/10.1038/nrg2100.
Patel PD, Bochar DA, Turner DL, Meng F, Mueller HM, Pontrello CG. Regulation of tryptophan hydroxylase-2 gene expression by a bipartite RE-1 silencer of transcription/neuron restrictive silencing factor (REST/NRSF) binding motif. J Biol Chem. 2007;282:26717–24. https://doi.org/10.1074/jbc.M705120200.
Patrick RP, Ames BN. Vitamine D hormone regulates serotonin synthesis. Part 1: relevance for autism. FASEB J. 2014;28:2398–413. https://doi.org/10.1096/fj.13-246546.
Scheuch K, Lautenschlager M, Grohmann M, Stahlberg S, Kirchheiner J, Zill P, Heinz A, Walther DJ, Priller J. Characterization of a functional promoter polymorphism of the human tryptophan hydroxylase 2 gene in serotonergic raphe neurons. Biol Psychiatry. 2007;62:1288–94. https://doi.org/10.1016/j.biopsych.2007.01.015.
Winge I, McKinney J, Haavik J. Tryptophan hydroxylase. In: JFP D’M, editor. Amino acids in human nutrition and health. Wallingford: CAB International; 2012. p. 150–72.
Walther DJ, Bader M. A unique central tryptophan hydroxylase isoform. Biochem Pharmacol. 2003;66:1673–80.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2018 Springer International Publishing AG
About this entry
Cite this entry
Nawa, Y., Colucci-D’Amato, L., Matsui, H. (2018). Tryptophan Hydroxylase 2. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101618
Download citation
DOI: https://doi.org/10.1007/978-3-319-67199-4_101618
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-67198-7
Online ISBN: 978-3-319-67199-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences