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Gene Review

TH  -  tyrosine hydroxylase

Canis lupus familiaris

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Disease relevance of TH


High impact information on TH

  • In addition, SPG-induced histofluorescence correlated significantly with NE uptake activity (r = .712, P < .001) and tyrosine hydroxylase immunoreactive profiles (r = .569, P < .001) in the right ventricles of RHF dogs and in both ventricles of LHF dogs [3].
  • NE uptake activity was measured using [3H]NE, and noradrenergic nerve profiles were visualized by glyoxylic acid (SPG)-induced histofluorescence and tyrosine hydroxylase immunocytochemical staining [3].
  • Chronic infusion of NE decreased heart rate in normal dogs but had no effect on either mean aortic pressure or left atrial pressure; like heart failure, it resulted in significant decreases in myocardial NE uptake activity and numbers of SPG-induced catecholaminergic histofluorescence and immunoreactive tyrosine hydroxylase profiles [3].
  • The results indicate that TOH phenotype is not expressed when the cells are born in the subependymal zone nor during their migration to the periglomerular region but only after they reached their final destination, the glomerular layer [4].
  • RESULTS: In protocol 1, the hearts from dogs with LSG electrical stimulation had a higher density of nerve fibers immunopositive to tyrosine hydroxylase, synaptophysin, and growth-associated protein-43 than those of normal control dogs (p < 0.01) [5].

Biological context of TH

  • The distribution of TH- and DDC-immunoreactive nerves in the renal cortex is compatible with existing functional evidence indicating that both dopaminergic and noradrenergic nerves are involved in the regulation of renal blood flow, tubular reabsorption and renin release [6].
  • In the present study we demonstrated that catecholamine is also a candidate neurotransmitter in the canine laryngeal afferent system using tyrosine hydroxylase (TH) immunochemistry in combination with retrograde labelling with cholera toxin B in subunit-conjugated gold (CTBG) [7].

Anatomical context of TH

  • METHODS: Corneal nerve fibers in normal dog eyes were labeled immunohistochemically with antibodies against protein gene product (PGP)-9.5, calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), and tyrosine hydroxylase (TH) [8].
  • Many TH- and neuropeptide Y (NPY)-immunoreactive fibers were arranged around the blood vessels [9].
  • The E-E group revealed some TH fibers extending across the arterial anastomosis toward the graft mesentery [10].
  • In dog ileum, axons containing immunoreactivity for tyrosine hydroxylase (TH) and for DOPA decarboxylase (DDC) invest the neurones of the enteric ganglia and are present around arterioles, in the deep plexus of the circular muscle and in the laminar propria of the mucosal villi [11].
  • Alternate sections in the caudate nucleus stained for acetylcholinesterase, TH, and terminal degeneration revealed that the areas of densest degeneration were localized to the matrix, thereby outlining areas of much lighter degeneration which were coincident with the patches [12].

Associations of TH with chemical compounds

  • RESULTS: More than 99% of all corneal PGP-9.5-immunoreactive (IR) nerves contained both CGRP and SP, approximately 30% contained TH, and none contained VIP [8].
  • Single toxic doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).HCl (2.5 mg/kg i.v.) and 4'-amino-MPTP.2HCl (22.5 mg/kg) induce loss of striatal dopamine (DA) and tyrosine hydroxylase (TH) activity and of nigral DA neurons in the dog [13].
  • Therefore, it is concluded that, of the concentrations of NSD-1015 tested, 0.1 microM is the optimum concentration to use in this preparation for studies designed to examine TH activity by measuring DOPA after the inhibition of AAAD [14].
  • Since the numbers and locations of TH- and PNMT-ir neurons in the C1 area of the RVLM and rostral LTF were virtually identical on adjacent sections, it can be implicitly inferred that the enzymes are co-localized to the same somata and that these neurons are capable of biosynthesizing adrenaline [15].
  • Release of 3,4-dihydroxyphenylalanine was calcium and frequency dependent, inhibited by a-m-L-p-tyrosine (an inhibitor of tyrosine hydroxylase) and augmented by 3-hydroxybenzylhydrazine (an inhibitor of aromatic amino acid decarboxylase) [16].

Co-localisations of TH


Other interactions of TH

  • In the celiac ganglion, virtually all cell bodies were positive for both galanin and TH; a large subpopulation of these cells were also positive for NPY [18].

Analytical, diagnostic and therapeutic context of TH

  • Immunohistochemistry results showed no significant indication of extrinsic reinnervation until 12 months, when TH fibers were observed in five of six dogs [10].
  • Two weeks after extrinsic denervation of the ileum, all TH staining was absent [11].
  • In the ischemic zone 5 h after LAD ligation, TH activity was lower than in corresponding anterior apical zones of S dogs (5.1 +/- 1.7 vs. 13.5 +/- 2.3 nmol.g-1.h-1) (P less than 0.05) with a tendency for greater decreases in endocardium than in epicardium [19].
  • Two types of cells were identified by PAP electron microscopy; TH-positive and TH-negative cells [20].
  • Immunoblot analysis of tissue samples taken from laser-treated regions demonstrated a 66% reduction in tyrosine hydroxylase, a sympathetic nerve-specific enzyme, as assessed by densitometry [21].


  1. Cre recombinase-mediated restoration of nigrostriatal dopamine in dopamine-deficient mice reverses hypophagia and bradykinesia. Hnasko, T.S., Perez, F.A., Scouras, A.D., Stoll, E.A., Gale, S.D., Luquet, S., Phillips, P.E., Kremer, E.J., Palmiter, R.D. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. Inhibition of myocardial tyrosine hydroxylase during myocardial ischemia. Vulliet, P.R., Buchl, S.J., Pelletier, Y. Proc. West. Pharmacol. Soc. (1985) [Pubmed]
  3. Cardiac noradrenergic nerve terminal abnormalities in dogs with experimental congestive heart failure. Himura, Y., Felten, S.Y., Kashiki, M., Lewandowski, T.J., Delehanty, J.M., Liang, C.S. Circulation (1993) [Pubmed]
  4. Postmitotic, postmigrational expression of tyrosine hydroxylase in olfactory bulb dopaminergic neurons. McLean, J.H., Shipley, M.T. J. Neurosci. (1988) [Pubmed]
  5. Long-term subthreshold electrical stimulation of the left stellate ganglion and a canine model of sudden cardiac death. Swissa, M., Zhou, S., Gonzalez-Gomez, I., Chang, C.M., Lai, A.C., Cates, A.W., Fishbein, M.C., Karagueuzian, H.S., Chen, P.S., Chen, L.S. J. Am. Coll. Cardiol. (2004) [Pubmed]
  6. The innervation of the renal cortex in the dog. An ultrastructural study. Ferguson, M., Ryan, G.B., Bell, C. Cell Tissue Res. (1988) [Pubmed]
  7. Tyrosine hydroxylase-immunoreactive cells in the nodose ganglion for the canine larynx. Uno, T., Hisa, Y., Tadaki, N., Okamura, H., Ibata, Y. Neuroreport (1996) [Pubmed]
  8. Morphology and neurochemistry of canine corneal innervation. Marfurt, C.F., Murphy, C.J., Florczak, J.L. Invest. Ophthalmol. Vis. Sci. (2001) [Pubmed]
  9. Neurochemical markers in the nervous plexus of the canine glottis. Yamamoto, Y., Atoji, Y., Suzuki, Y. J. Auton. Nerv. Syst. (1998) [Pubmed]
  10. Extrinsic intestinal reinnervation after canine small bowel autotransplantation. Sugitani, A., Reynolds, J.C., Tsuboi, M., Todo, S. Surgery (1998) [Pubmed]
  11. Distribution and origin of aminergic neurones in dog small intestine. Mann, R., Bell, C. J. Auton. Nerv. Syst. (1993) [Pubmed]
  12. MPTP produces a pattern of nigrostriatal degeneration which coincides with the mosaic organization of the caudate nucleus. Turner, B.H., Wilson, J.S., McKenzie, J.C., Richtand, N. Brain Res. (1988) [Pubmed]
  13. Prolonged alterations in canine striatal dopamine metabolism following subtoxic doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 4'-amino-MPTP are linked to the persistence of pyridinium metabolites. Johannessen, J.N., Sobotka, T.J., Weise, V.K., Markey, S.P. J. Neurochem. (1991) [Pubmed]
  14. Inhibition of aromatic L-amino acid decarboxylase under physiological conditions: optimization of 3-hydroxybenzylhydrazine concentration to prevent concurrent inhibition of monoamine oxidase. Hunter, L.W., Rorie, D.K., Tyce, G.M. Biochem. Pharmacol. (1993) [Pubmed]
  15. Organization of presumptive catecholamine-synthesizing neurons in the canine medulla oblongata. Dormer, K.J., Anwar, M., Ashlock, S.R., Ruggiero, D.A. Brain Res. (1993) [Pubmed]
  16. Dihydroxyphenylalanine and dopamine are released from portal vein together with noradrenaline and dihydroxyphenylglycol during nerve stimulation. Hunter, L.W., Rorie, D.K., Tyce, G.M. J. Neurochem. (1992) [Pubmed]
  17. The canine sympathetic neuropeptide galanin: a neurotransmitter in pancreas, a neuromodulator in liver. Taborsky, G.J., Dunning, B.E., Havel, P.J., Ahren, B., Kowalyk, S., Boyle, M.R., Verchere, C.B., Baskin, D.G., Mundinger, T.O. Horm. Metab. Res. (1999) [Pubmed]
  18. Galanin is co-localized with noradrenaline and neuropeptide Y in dog pancreas and celiac ganglion. Ahrén, B., Böttcher, G., Kowalyk, S., Dunning, B.E., Sundler, F., Taborsky, G.J. Cell Tissue Res. (1990) [Pubmed]
  19. Tyrosine hydroxylase and choline acetyltransferase activities in ischemic canine heart. Schmid, P.G., Greif, B.J., Lund, D.D., Roskoski, R. Am. J. Physiol. (1982) [Pubmed]
  20. Immunohistocytochemical and immunofluorescent localization of catecholamine-synthesizing enzymes in the carotid body of the bat and dog. Karasawa, N., Kondo, Y., Nagatsu, I. Archivum histologicum Japonicum. Nippon soshikigaku kiroku. (1982) [Pubmed]
  21. Nontransmural laser treatment incompletely denervates canine myocardium. Kwong, K.F., Schuessler, R.B., Kanellopoulos, G.K., Saffitz, J.E., Sundt, T.M. Circulation (1998) [Pubmed]
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