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...
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References
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. doi: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. doi: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. doi: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. doi: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. doi: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. doi: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. doi: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. doi: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. doi: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. doi:10.1093/gbe/evu072.
Ooi L, Wood IC. Chromatin crosstalk in development and disease: lessons from REST. Hum Mutat. 2009;30:787–94. doi: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. doi: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. doi: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. doi: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.
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Nawa, Y., Colucci-D’Amato, L., Matsui, H. (2016). Tryptophan Hydroxylase 2. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101618-1
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DOI: https://doi.org/10.1007/978-1-4614-6438-9_101618-1
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