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Gene Review

Th  -  tyrosine hydroxylase

Mus musculus

Synonyms: TH, Tyrosine 3-hydroxylase, Tyrosine 3-monooxygenase
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Disease relevance of Th

  • The terminals of preganglionic axons in the ciliary ganglion exhibited not only immunoreactivity for ChAT, but also for TH and contained stores of endogenous catecholamine [1].
  • The paradoxical hyperdopaminergia in the DAT KO mice despite a marked decrease in TH and dopamine levels suggests a parallel to Parkinson's disease implying that blockade of DAT may be beneficial in this condition [2].
  • The present results suggest (1) that the postnatal increases in adrenal TH mRNA levels are not directly due to hypoxia at birth, and (2) that the increased mortality seen after hypoxia in nicotine pups concurs with a perturbed LC function in these animals [3].
  • The preferential differentiation of T helper (Th) cells to Th1 or Th2 subsets is important with respect to susceptibility or resistance to particular infections, or to autoimmune diseases and allergic diseases [4].
  • Failure of PACAP-deficient mice to adequately counterregulate plasma glucose levels could be accounted for by impaired long-term secretion of epinephrine, secondary to a lack of induction of tyrosine hydroxylase, normally occurring after insulin hypoglycemia in wild-type mice, and a consequent depletion of adrenomedullary epinephrine stores [5].

Psychiatry related information on Th


High impact information on Th


Chemical compound and disease context of Th


Biological context of Th


Anatomical context of Th


Associations of Th with chemical compounds

  • The molecular interaction between the Y(1) receptor and TH was demonstrated by the fact that NPY markedly inhibited the forskolin-induced luciferin activity in Y(1) receptor-expressing SK-N-MC cells transfected with a TH promoter sequence [26].
  • Immunoblot analysis revealed that SK elicited a parallel increase in TH enzyme protein [21].
  • Although diminished in magnitude, a sweat response to pilocarpine was also noted in TH -/- mice at P21 [27].
  • Cyclin-dependent kinase 5 phosphorylates serine 31 of tyrosine hydroxylase and regulates its stability [28].
  • Finally, phospho-Ser31 TH levels were increased in dopaminergic neurons of rats trained to chronically self-administer cocaine [29].

Physical interactions of Th


Enzymatic interactions of Th


Co-localisations of Th


Regulatory relationships of Th


Other interactions of Th

  • Wnt-3a promoted the proliferation of precursor cells expressing the orphan nuclear receptor-related factor 1 (Nurr1) but did not increase the number of tyrosine hydroxylase-positive neurons [42].
  • The present study was designed to test whether PRL replacement during the early postnatal period would increase DA and TH expression in dwarfs [43].
  • The present study supports the hypothesis that alpha-synuclein functions as a molecular chaperone protein that regulates the phosphorylation state of TH in a substrate and activity-dependent manner [37].
  • TH appears in these neurons at E11.5, consistent with a putative role of Pitx3 in TH transcription [38].
  • Involvement of leukemia inhibitory factor in the increases in galanin and vasoactive intestinal peptide mRNA and the decreases in neuropeptide Y and tyrosine hydroxylase mRNA in sympathetic neurons after axotomy [44].

Analytical, diagnostic and therapeutic context of Th


  1. Catecholaminergic properties of cholinergic neurons and synapses in adult rat ciliary ganglion. Landis, S.C., Jackson, P.C., Fredieu, J.R., Thibault, J. J. Neurosci. (1987) [Pubmed]
  2. Differential regulation of tyrosine hydroxylase in the basal ganglia of mice lacking the dopamine transporter. Jaber, M., Dumartin, B., Sagné, C., Haycock, J.W., Roubert, C., Giros, B., Bloch, B., Caron, M.G. Eur. J. Neurosci. (1999) [Pubmed]
  3. Perinatal nicotine attenuates the hypoxia-induced up-regulation of tyrosine hydroxylase and galanin mRNA in locus ceruleus of the newborn mouse. Wickström, H.R., Mas, C., Simonneau, M., Holgert, H., Hökfelt, T., Lagercrantz, H. Pediatr. Res. (2002) [Pubmed]
  4. Potentiation of antigen-specific, Th1 immune responses by multiple DNA vaccination with an ovalbumin/interferon-gamma hybrid construct. Lim, Y.S., Kang, B.Y., Kim, E.J., Kim, S.H., Hwang, S.Y., Kim, T.S. Immunology (1998) [Pubmed]
  5. Pituitary adenylate cyclase-activating polypeptide is a sympathoadrenal neurotransmitter involved in catecholamine regulation and glucohomeostasis. Hamelink, C., Tjurmina, O., Damadzic, R., Young, W.S., Weihe, E., Lee, H.W., Eiden, L.E. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  6. Differential expression of monoamine oxidase A, serotonin transporter, tyrosine hydroxylase and norepinephrine transporter mRNA by anorexia mutation and food deprivation. Jahng, J.W., Houpt, T.A., Joh, T.H., Son, J.H. Brain Res. Dev. Brain Res. (1998) [Pubmed]
  7. Analysis of cellular, transgenic and human models of Huntington's disease reveals tyrosine hydroxylase alterations and substantia nigra neuropathology. Yohrling, G.J., Jiang, G.C., DeJohn, M.M., Miller, D.W., Young, A.B., Vrana, K.E., Cha, J.H. Brain Res. Mol. Brain Res. (2003) [Pubmed]
  8. Role of the biogenic amines in the reversal of cycloheximide-induced amnesia. Quartermain, D., Botwinick, C.Y. Journal of comparative and physiological psychology. (1975) [Pubmed]
  9. A functional idiotypic network of T helper cells and antibodies, limited to the compartment of "naturally" activated lymphocytes in normal mice. Coutinho, A., Marquez, C., Araujo, P.M., Pereira, P., Toribio, M.L., Marcos, M.A., Martinez, C. Eur. J. Immunol. (1987) [Pubmed]
  10. Synergistic effects of melatonin and deprenyl against MPTP-induced mitochondrial damage and DA depletion. Khaldy, H., Escames, G., León, J., Bikjdaouene, L., Acuña-Castroviejo, D. Neurobiol. Aging (2003) [Pubmed]
  11. Dopamine is required for hyperphagia in Lep(ob/ob) mice. Szczypka, M.S., Rainey, M.A., Palmiter, R.D. Nat. Genet. (2000) [Pubmed]
  12. Autoimmune T cells: immune recognition of normal and variant peptide epitopes and peptide-based therapy. Urban, J.L., Horvath, S.J., Hood, L. Cell (1989) [Pubmed]
  13. Proliferation, senescence, and neoplastic progression of beta cells in hyperplasic pancreatic islets. Teitelman, G., Alpert, S., Hanahan, D. Cell (1988) [Pubmed]
  14. Concomitant elevation of tyrosine hydroxylase and dopamine beta-hydroxylase by cyclic AMP in cultured mouse neuroblastoma cells. Waymire, J.C., Gilmer-Waymire, K., Boehme, R.E. J. Neurochem. (1978) [Pubmed]
  15. Inability to demonstrate hydroxylation of tyrosine by murine melanoma "tyrosinase" (L-DOPA oxidase), using the tritiated water assay technique. Shapiro, H.C., Edelstein, L.M., Patel, R.P., Okun, M.R., Blackburn, M., Snyder, M., Brennan, T., Wilgram, G. J. Invest. Dermatol. (1979) [Pubmed]
  16. Characteristics of tyrosinase in B16 melanoma. White, R., Hu, F. J. Invest. Dermatol. (1977) [Pubmed]
  17. Localization of insulin-2 (Ins-2) and the obesity mutant tubby (tub) to distinct regions of mouse chromosome 7. Jones, J.M., Meisler, M.H., Seldin, M.F., Lee, B.K., Eicher, E.M. Genomics (1992) [Pubmed]
  18. The homeobox gene Phox2b is essential for the development of autonomic neural crest derivatives. Pattyn, A., Morin, X., Cremer, H., Goridis, C., Brunet, J.F. Nature (1999) [Pubmed]
  19. Engrailed genes are cell-autonomously required to prevent apoptosis in mesencephalic dopaminergic neurons. Albéri, L., Sgadò, P., Simon, H.H. Development (2004) [Pubmed]
  20. Catecholamine synthesis is mediated by tyrosinase in the absence of tyrosine hydroxylase. Rios, M., Habecker, B., Sasaoka, T., Eisenhofer, G., Tian, H., Landis, S., Chikaraishi, D., Roffler-Tarlov, S. J. Neurosci. (1999) [Pubmed]
  21. Presynaptic transmitters and depolarizing influences regulate development of the substantia nigra in culture. Friedman, W.J., Dreyfus, C.F., McEwen, B., Black, I.B. J. Neurosci. (1988) [Pubmed]
  22. Functionally antagonistic interactions between the TrkA and p75 neurotrophin receptors regulate sympathetic neuron growth and target innervation. Kohn, J., Aloyz, R.S., Toma, J.G., Haak-Frendscho, M., Miller, F.D. J. Neurosci. (1999) [Pubmed]
  23. Neurochemical and immunocytochemical studies of catecholamine system in the brindled mouse. Satoh, J., Irino, M., Martin, P.M., Mailman, R.B., Suzuki, K. J. Neuropathol. Exp. Neurol. (1991) [Pubmed]
  24. Differential effects of l-DOPA on monoamine metabolism, cell survival and glutathione production in midbrain neuronal-enriched cultures from parkin knockout and wild-type mice. Casarejos, M.J., Solano, R.M., Menéndez, J., Rodríguez-Navarro, J.A., Correa, C., García de Yébenes, J., Mena, M.A. J. Neurochem. (2005) [Pubmed]
  25. Effects of systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to mice on tyrosine hydroxylase, L-3,4-dihydroxyphenylalanine decarboxylase, dopamine beta-hydroxylase, and monoamine oxidase activities in the striatum and hypothalamus. Mogi, M., Harada, M., Kojima, K., Kiuchi, K., Nagatsu, T. J. Neurochem. (1988) [Pubmed]
  26. Deletion of the neuropeptide Y (NPY) Y1 receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion. Cavadas, C., Céfai, D., Rosmaninho-Salgado, J., Vieira-Coelho, M.A., Moura, E., Busso, N., Pedrazzini, T., Grand, D., Rotman, S., Waeber, B., Aubert, J.F., Grouzmann, E. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  27. Norepinephrine facilitates the development of the murine sweat response but is not essential. Tafari, A.T., Thomas, S.A., Palmiter, R.D. J. Neurosci. (1997) [Pubmed]
  28. Cyclin-dependent kinase 5 phosphorylates serine 31 of tyrosine hydroxylase and regulates its stability. Moy, L.Y., Tsai, L.H. J. Biol. Chem. (2004) [Pubmed]
  29. Identification of tyrosine hydroxylase as a physiological substrate for Cdk5. Kansy, J.W., Daubner, S.C., Nishi, A., Sotogaku, N., Lloyd, M.D., Nguyen, C., Lu, L., Haycock, J.W., Hope, B.T., Fitzpatrick, P.F., Bibb, J.A. J. Neurochem. (2004) [Pubmed]
  30. Alpha-synuclein activation of protein phosphatase 2A reduces tyrosine hydroxylase phosphorylation in dopaminergic cells. Peng, X., Peng, X.M., Tehranian, R., Dietrich, P., Stefanis, L., Perez, R.G. J. Cell. Sci. (2005) [Pubmed]
  31. Pattern of levodopa-induced striatal changes is different in normal and MPTP-lesioned mice. Gross, C.E., Ravenscroft, P., Dovero, S., Jaber, M., Bioulac, B., Bezard, E. J. Neurochem. (2003) [Pubmed]
  32. Hyperdopaminergia and altered locomotor activity in GABAB1-deficient mice. Vacher, C.M., Gassmann, M., Desrayaud, S., Challet, E., Bradaia, A., Hoyer, D., Waldmeier, P., Kaupmann, K., Pévet, P., Bettler, B. J. Neurochem. (2006) [Pubmed]
  33. Characterization of a concanavalin A supernatant-derived idiotype-specific T helper cell factor. Bowen, M.B., Pruchno, C., Bellone, C.J. J. Immunol. (1986) [Pubmed]
  34. Enhanced expression of Ca2+ channel alpha1A and beta4 subunits and phosphorylated tyrosine hydroxylase in the adrenal gland of N-type Ca2+ channel alpha1B subunit-deficient mice with a CBA/JN genetic background. Takahashi, E., Nagasu, T. Comp. Med. (2006) [Pubmed]
  35. A confocal microscopic study of gonadotropin-releasing hormone (GnRH) neuron inputs to dopaminergic neurons containing estrogen receptor alpha in the arcuate nucleus of GnRH-green fluorescent protein transgenic mice. Mitchell, V., Loyens, A., Spergel, D.J., Flactif, M., Poulain, P., Tramu, G., Beauvillain, J.C. Neuroendocrinology (2003) [Pubmed]
  36. Evidence that brain-derived neurotrophic factor from presynaptic nerve terminals regulates the phenotype of calbindin-containing neurons in the lateral septum. Fawcett, J.P., Alonso-Vanegas, M.A., Morris, S.J., Miller, F.D., Sadikot, A.F., Murphy, R.A. J. Neurosci. (2000) [Pubmed]
  37. Substrate-mediated enhancement of phosphorylated tyrosine hydroxylase in nigrostriatal dopamine neurons: evidence for a role of alpha-synuclein. Drolet, R.E., Behrouz, B., Lookingland, K.J., Goudreau, J.L. J. Neurochem. (2006) [Pubmed]
  38. Pitx3 activates mouse tyrosine hydroxylase promoter via a high-affinity binding site. Lebel, M., Gauthier, Y., Moreau, A., Drouin, J. J. Neurochem. (2001) [Pubmed]
  39. Neural precursors derived from embryonic stem cells, but not those from fetal ventral mesencephalon, maintain the potential to differentiate into dopaminergic neurons after expansion in vitro. Chung, S., Shin, B.S., Hwang, M., Lardaro, T., Kang, U.J., Isacson, O., Kim, K.S. Stem Cells (2006) [Pubmed]
  40. Prolactin gene disruption does not compromise differentiation of tuberoinfundibular dopaminergic neurons. Phelps, C.J., Horseman, N.D. Neuroendocrinology (2000) [Pubmed]
  41. Antagonists of the neurokinin-1 or dopamine D1 receptors confer protection from methamphetamine on dopamine terminals of the mouse striatum. Angulo, J.A., Angulo, N., Yu, J. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  42. Differential regulation of midbrain dopaminergic neuron development by Wnt-1, Wnt-3a, and Wnt-5a. Castelo-Branco, G., Wagner, J., Rodriguez, F.J., Kele, J., Sousa, K., Rawal, N., Pasolli, H.A., Fuchs, E., Kitajewski, J., Arenas, E. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  43. Prolactin replacement during development prevents the dopaminergic deficit in hypothalamic arcuate nucleus in prolactin-deficient Ames dwarf mice. Romero, M.I., Phelps, C.J. Endocrinology (1993) [Pubmed]
  44. Involvement of leukemia inhibitory factor in the increases in galanin and vasoactive intestinal peptide mRNA and the decreases in neuropeptide Y and tyrosine hydroxylase mRNA in sympathetic neurons after axotomy. Sun, Y., Zigmond, R.E. J. Neurochem. (1996) [Pubmed]
  45. Reinnervation of transplanted pancreatic islets. A comparison among islets implanted into the kidney, spleen, and liver. Korsgren, O., Jansson, L., Andersson, A., Sundler, F. Transplantation (1993) [Pubmed]
  46. Morphological and functional in vitro and in vivo characterization of the mouse corpus cavernosum. Mizusawa, H., Hedlund, P., Håkansson, A., Alm, P., Andersson, K.E. Br. J. Pharmacol. (2001) [Pubmed]
  47. Induction of midbrain dopaminergic neurons from primate embryonic stem cells by coculture with sertoli cells. Yue, F., Cui, L., Johkura, K., Ogiwara, N., Sasaki, K. Stem Cells (2006) [Pubmed]
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