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Gene Review

Th  -  tyrosine hydroxylase

Rattus norvegicus

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


Psychiatry related information on Th


High impact information on Th


Chemical compound and disease context of Th


Biological context of Th

  • Preloading of neurons with p62-pep (a peptide containing consenses of mitogen-activated protein kinase in p62) resulted in a loss of Ang II-induced p62 phosphorylation and stimulation of NET and TH messenger RNA levels [19].
  • Mapping the TH promoter showed that the putative half estrogen response element (ERE) motif at - 675, as well as the activation protein 1 motif at - 205, were not required for response to E2 with either ER [20].
  • Thus, three different signal transduction systems appear to mediate the physiological regulation of tyrosine hydroxylase phosphorylation at three different sites [21].
  • Finally, the enhanced TH promoter activity was competitively attenuated by expression of a plasmid containing the ATF-2 transactivation domain [22].
  • First, by using reporter constructs, we found that the transcription mediated by cAMP-responsive element (CRE) was selectively enhanced in the V-1 cells, and TH promoter activity was totally dependent on the CRE in the promoter region of the TH gene [22].

Anatomical context of Th

  • Furthermore, depletion of MARCKS by MARCKS-AON treatment of neurons resulted in a significant decrease in Ang II-stimulated accumulation of TH and DbetaH immunoreactivities and [3H]NE uptake activity in synaptosomes [23].
  • A similar decline in the ratio of TH mRNA-containing to TH-immunoreactive cells was not observed in sympathetic ganglia [24].
  • PC12 cells, transiently co-transfected with expression vector for ERalpha or ERbeta, and luciferase gene under control of the TH promoter, were treated with 17 beta-estradiol (E2) [20].
  • In contrast, TH and DBH mRNA levels in the SCG, but not in adrenal medulla, were elevated by ACTH administration, similar to the levels attained after immobilization [25].
  • Repeated stress elevated expression of all the genes studied and increased TH immunoreactivity in both ganglia [25].

Associations of Th with chemical compounds

  • Moreover, E2 attenuated the increase in TH transcription seen with cyclic AMP analogs [20].
  • Thus, TH is transcriptionally regulated by estradiol in opposite directions depending on ER subtype [20].
  • The results show that there was no difference in TH mRNA content; however, DBH mRNA levels in areas A1, A2, and C1 of the middle-aged animals did not rise during the surge as was observed in the young animals [26].
  • Prolonged cortisol administration failed to alter the mRNA levels of TH, DBH, and NPY in control animals but attenuated the response to stress [25].
  • The increase in TH may reflect a compensatory response of dopaminergic neurons to upregulate their synthesizing capacity and increase the efficiency of dopamine neurotransmission chronically after TBI [2].

Physical interactions of Th


Enzymatic interactions of Th


Co-localisations of Th


Regulatory relationships of Th


Other interactions of Th

  • These studies demonstrate that NGF can signal retrogradely to mediate the induction of TH and p75NTR mRNAs [44].
  • Angiotensin II (Ang II) interaction with the neuronal AT1 receptor results in a chronic stimulation of neuromodulation that involves the expression of norepinephrine transporter (NET) and tyrosine hydroxylase (TH) [19].
  • We also show that some of the effects of pVHL on activity of the TH promoter are mediated through HIFs [1].
  • Isolation stress increases tyrosine hydroxylase mRNA in the locus coeruleus and midbrain and decreases proenkephalin mRNA in the striatum and nucleus accumbens [45].
  • Ovaries in both PCO and PCO anti-NGF groups decreased in size as well as in number and size of corpora lutea. mRNA expression of alpha1a-AR and TrkA in the ovaries was lower, whereas expression of alpha1b- and alpha1d-AR and TH was higher, in the PCO group than in controls [46].

Analytical, diagnostic and therapeutic context of Th

  • After Day E12 TH mRNA cannot be detected in enteric or vagal cells by in situ hybridization; nevertheless, TH immunoreactivity continues to be present through Day E14 [24].
  • Our results show a severalfold increase in the relative abundance of TH and NPY mRNAs in response to a single immobilization [25].
  • No alterations in DBH levels were observed by Western blot at any time point examined, but there was a significant increase in TH expression 28 days after TBI (optical density 334 +/- 68% or 3.3-fold, ipsilateral and 218 +/- 39% or 2.2-fold, contralateral) relative to the sham controls [2].
  • The intensity of both the TH and DBH immunofluorescence decreased as the glands and their innervation developed [47].
  • Semi-quantitative RT-PCR and quantitative immunoblotting experiments revealed that GAL had no effect on TH mRNA levels in VM cultures but reduced TH protein [39].


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  2. Tyrosine hydroxylase, but not dopamine beta-hydroxylase, is increased in rat frontal cortex after traumatic brain injury. Yan, H.Q., Kline, A.E., Ma, X., Hooghe-Peters, E.L., Marion, D.W., Dixon, C.E. Neuroreport (2001) [Pubmed]
  3. Gene expression of catecholamine synthesizing enzymes in A5 cell group and modulation of tyrosine hydroxylase mRNA by immobilization stress. Micutkova, L., Kiss, A., Filipenko, M., Rychkova, N., Krizanova, O., Palkovits, M., Kvetnansky, R. Endocrine regulations. (2001) [Pubmed]
  4. Identification and cell type specificity of the tyrosine hydroxylase gene promoter. Harrington, C.A., Lewis, E.J., Krzemien, D., Chikaraishi, D.M. Nucleic Acids Res. (1987) [Pubmed]
  5. Heightened transcription for enzymes involved in norepinephrine biosynthesis in the rat locus coeruleus by immobilization stress. Serova, L.I., Nankova, B.B., Feng, Z., Hong, J.S., Hutt, M., Sabban, E.L. Biol. Psychiatry (1999) [Pubmed]
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  7. Stress-induced increase in urinary isatin excretion in rats: reversal by both dexamethasone and alpha-methyl-P-tyrosine. Tozawa, Y., Ueki, A., Manabe, S., Matsushima, K. Biochem. Pharmacol. (1998) [Pubmed]
  8. The effects of electroconvulsive shock on catecholamine function in the locus ceruleus and hippocampus. Weiner, N., Hossain, M.A., Masserano, J.M. J. Neural Transm. Suppl. (1991) [Pubmed]
  9. Diurnal variations in the motor activity of the rat: effects of inhibitors of the catecholamine synthesis. Lemmer, B., Berger, T. Naunyn Schmiedebergs Arch. Pharmacol. (1978) [Pubmed]
  10. Nerve growth factor mediates phosphorylation of specific proteins. Halegoua, S., Patrick, J. Cell (1980) [Pubmed]
  11. Testis-derived Sertoli cells have a trophic effect on dopamine neurons and alleviate hemiparkinsonism in rats. Sanberg, P.R., Borlongan, C.V., Othberg, A.I., Saporta, S., Freeman, T.B., Cameron, D.F. Nat. Med. (1997) [Pubmed]
  12. Mesencephalic dopaminergic neurons protected by GDNF from axotomy-induced degeneration in the adult brain. Beck, K.D., Valverde, J., Alexi, T., Poulsen, K., Moffat, B., Vandlen, R.A., Rosenthal, A., Hefti, F. Nature (1995) [Pubmed]
  13. Pattern of presynaptic nerve activity can determine the type of neurotransmitter regulating a postsynaptic event. Ip, N.Y., Zigmond, R.E. Nature (1984) [Pubmed]
  14. The response of the tyrosine hydroxylase gene to cyclic AMP is mediated by two cyclic AMP-response elements. Best, J.A., Chen, Y., Piech, K.M., Tank, A.W. J. Neurochem. (1995) [Pubmed]
  15. Angiotensin II AT(1) and AT(2) receptors contribute to maintain basal adrenomedullary norepinephrine synthesis and tyrosine hydroxylase transcription. Jezova, M., Armando, I., Bregonzio, C., Yu, Z.X., Qian, S., Ferrans, V.J., Imboden, H., Saavedra, J.M. Endocrinology (2003) [Pubmed]
  16. Gender differences in hypothalamic tyrosine hydroxylase and alpha(2)-adrenoceptor subtype gene expression in cafeteria diet-induced hypertension and consequences of neonatal androgenization. Plut, C., Ribiere, C., Giudicelli, Y., Dausse, J.P. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  17. Birth-related up-regulation of mRNA encoding tyrosine hydroxylase, dopamine beta-hydroxylase, neuropeptide tyrosine, and prepro-enkephalin in rat adrenal medulla is dependent on postnatal oxygenation. Holgert, H., Pequignot, J.M., Lagercrantz, H., Hökfelt, T. Pediatr. Res. (1995) [Pubmed]
  18. Levodopa-responsive infantile parkinsonism due to a novel mutation in the tyrosine hydroxylase gene and exacerbation by viral infections. Diepold, K., Schütz, B., Rostasy, K., Wilken, B., Hougaard, P., Güttler, F., Romstad, A., Birk Møller, L. Mov. Disord. (2005) [Pubmed]
  19. Angiotensin II-induced nuclear targeting of the angiotensin type 1 (AT1) receptor in brain neurons. Lu, D., Yang, H., Shaw, G., Raizada, M.K. Endocrinology (1998) [Pubmed]
  20. Transcriptional regulation of tyrosine hydroxylase by estrogen: opposite effects with estrogen receptors alpha and beta and interactions with cyclic AMP. Maharjan, S., Serova, L., Sabban, E.L. J. Neurochem. (2005) [Pubmed]
  21. Tyrosine hydroxylase in rat brain dopaminergic nerve terminals. Multiple-site phosphorylation in vivo and in synaptosomes. Haycock, J.W., Haycock, D.A. J. Biol. Chem. (1991) [Pubmed]
  22. Identification of ATF-2 as a transcriptional regulator for the tyrosine hydroxylase gene. Suzuki, T., Yamakuni, T., Hagiwara, M., Ichinose, H. J. Biol. Chem. (2002) [Pubmed]
  23. Regulation of angiotensin II-induced neuromodulation by MARCKS in brain neurons. Lu, D., Yang, H., Lenox, R.H., Raizada, M.K. J. Cell Biol. (1998) [Pubmed]
  24. Transiently catecholaminergic (TC) cells in the bowel of the fetal rat: precursors of noncatecholaminergic enteric neurons. Baetge, G., Pintar, J.E., Gershon, M.D. Dev. Biol. (1990) [Pubmed]
  25. Immobilization stress elevates gene expression for catecholamine biosynthetic enzymes and some neuropeptides in rat sympathetic ganglia: effects of adrenocorticotropin and glucocorticoids. Nankova, B., Kvetnansky, R., Hiremagalur, B., Sabban, B., Rusnak, M., Sabban, E.L. Endocrinology (1996) [Pubmed]
  26. Expression of estrogen receptor-alpha and cFos in norepinephrine and epinephrine neurons of young and middle-aged rats during the steroid-induced luteinizing hormone surge. Temel, S., Lin, W., Lakhlani, S., Jennes, L. Endocrinology (2002) [Pubmed]
  27. Effect of 1,2,3,4,-tetrahydroisoquinoline administration under conditions of CYP2D inhibition on dopamine metabolism, level of tyrosine hydroxylase protein and the binding of [3H]GBR 12,935 to dopamine transporter in the rat nigrostriatal, dopaminergic system. Lorenc-Koci, E., Antkiewicz-Michaluk, L., Wardas, J., Zapała, M., Wierońska, J. Brain Res. (2004) [Pubmed]
  28. AP-1 complex and c-fos transcription are involved in TPA provoked and trans-synaptic inductions of the tyrosine hydroxylase gene: insights into long-term regulatory mechanisms. Icard-Liepkalns, C., Biguet, N.F., Vyas, S., Robert, J.J., Sassone-Corsi, P., Mallet, J. J. Neurosci. Res. (1992) [Pubmed]
  29. Hypoxia-induced protein binding to O2-responsive sequences on the tyrosine hydroxylase gene. Norris, M.L., Millhorn, D.E. J. Biol. Chem. (1995) [Pubmed]
  30. Spike-and-wave neocortical patterns in rats: genetic and aminergic control. Buzsáki, G., Laszlovszky, I., Lajtha, A., Vadász, C. Neuroscience (1990) [Pubmed]
  31. Neurotensin increases tyrosine hydroxylase messenger RNA-positive neurons in substantia nigra after retrograde axonal transport. Burgevin, M.C., Castel, M.N., Quarteronet, D., Chevet, T., Laduron, P.M. Neuroscience (1992) [Pubmed]
  32. Phosphorylation of tyrosine hydroxylase on at least three sites in rat pheochromocytoma PC12 cells treated with 56 mM K+: determination of the sites on tyrosine hydroxylase phosphorylated by cyclic AMP-dependent and calcium/calmodulin-dependent protein kinases. Tachikawa, E., Tank, A.W., Yanagihara, N., Mosimann, W., Weiner, N. Mol. Pharmacol. (1986) [Pubmed]
  33. Death of dopaminergic neurons in vitro and in nigral grafts: reevaluating the role of caspase activation. Hurelbrink, C.B., Armstrong, R.J., Luheshi, L.M., Dunnett, S.B., Rosser, A.E., Barker, R.A. Exp. Neurol. (2001) [Pubmed]
  34. Sexually dimorphic expression of estrogen receptor beta in the anteroventral periventricular nucleus of the rat preoptic area: implication in luteinizing hormone surge. Orikasa, C., Kondo, Y., Hayashi, S., McEwen, B.S., Sakuma, Y. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  35. Tyrosine hydroxylase and neuropeptide Y are increased in ciliary ganglia of sympathectomized rats. Tyrrell, S., Siegel, R.E., Landis, S.C. Neuroscience (1992) [Pubmed]
  36. The innervation of the immature rat ovary by calcitonin gene-related peptide. Calka, J., McDonald, J.K., Ojeda, S.R. Biol. Reprod. (1988) [Pubmed]
  37. Evidence for coexistence of GABA and dopamine in neurons of the rat olfactory bulb. Gall, C.M., Hendry, S.H., Seroogy, K.B., Jones, E.G., Haycock, J.W. J. Comp. Neurol. (1987) [Pubmed]
  38. Synaptotagmin I is present mainly in autonomic and sensory neurons of the rat peripheral nervous system. Li, J.Y., Jahn, R., Dahlström, A. Neuroscience (1994) [Pubmed]
  39. Galanin inhibits tyrosine hydroxylase expression in midbrain dopaminergic neurons. Counts, S.E., McGuire, S.O., Sortwell, C.E., Crawley, J.N., Collier, T.J., Mufson, E.J. J. Neurochem. (2002) [Pubmed]
  40. Specification of neurotransmitter identity by Phox2 proteins in neural crest stem cells. Lo, L., Morin, X., Brunet, J.F., Anderson, D.J. Neuron (1999) [Pubmed]
  41. Urocortin 2 induces tyrosine hydroxylase phosphorylation in PC12 cells. Nemoto, T., Mano-Otagiri, A., Shibasaki, T. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  42. Glial cell line-derived neurotrophic factor modulates ischemia-induced tyrosine hydroxylase expression in rat hippocampus. Miyazaki, H., Ono, T., Okuma, Y., Nagashima, K., Nomura, Y. Eur. J. Neurosci. (2000) [Pubmed]
  43. Semichronic inhibition of glutathione reductase promotes oxidative damage to proteins and induces both transcription and translation of tyrosine hydroxylase in the nigrostriatal system. Romero-Ramos, M., Venero, J.L., Garcia-Rodriguez, S., Ayala, A., Machado, A., Cano, J. Free Radic. Res. (2003) [Pubmed]
  44. Spatial regulation of neuronal gene expression in response to nerve growth factor. Toma, J.G., Rogers, D., Senger, D.L., Campenot, R.B., Miller, F.D. Dev. Biol. (1997) [Pubmed]
  45. Isolation stress increases tyrosine hydroxylase mRNA in the locus coeruleus and midbrain and decreases proenkephalin mRNA in the striatum and nucleus accumbens. Angulo, J.A., Printz, D., Ledoux, M., McEwen, B.S. Brain Res. Mol. Brain Res. (1991) [Pubmed]
  46. Effect of anti-NGF on ovarian expression of alpha1- and beta2-adrenoceptors, TrkA, p75NTR, and tyrosine hydroxylase in rats with steroid-induced polycystic ovaries. Manni, L., Holmäng, A., Cajander, S., Lundeberg, T., Aloe, L., Stener-Victorin, E. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  47. Evidence for neurotransmitter plasticity in vivo. II. Immunocytochemical studies of rat sweat gland innervation during development. Landis, S.C., Siegel, R.E., Schwab, M. Dev. Biol. (1988) [Pubmed]
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