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Gene Review

TH  -  tyrosine hydroxylase

Sus scrofa

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Disease relevance of TH


Psychiatry related information on TH

  • Pig anti-(BALB/c antinuclease) anti-idiotypic antibodies (pig anti-BALB/c Id) react only with TH of nuclease-primed BALB/c and not with B10.D2 animals [5].

High impact information on TH

  • In both strains, such immunization with nuclease also leads to the production of splenic T helper cells (TH), which provide nuclease-specific help in an in vitro plaque-forming cell response to nuclease-TNP [5].
  • The absence of absolute reductions in choline acetyltransferase activity in hypertrophied and failing ventricle contrasts strikingly with the previously reported reductions in tyrosine hydroxylase, which is rate limiting in sympathetic neurotransmitter biosynthesis [6].
  • Dopamine-containing neurons, identified immunocytochemically by the presence of tyrosine hydroxylase, had a mean length-to-width profile of 14.9 +/- 4.4 x 11.5 +/- 3.1 microns (N = 14) [7].
  • Another 50% of the nerve cell bodies contained immunoreactivity (IR) to dopamine-beta-hydroxylase (DBH), but did not have any other characteristics of noradrenergic neurons; they did not contain detectable catecholamines, or IR to dopa decarboxylase (DDC) or tyrosine (TH) hydroxylase, nor did they take up exogenous catecholamines [8].
  • For comparison, the ganglion was also studied using antisera against the 2 catecholamine-synthesizing enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH) [9].

Biological context of TH

  • TH inhibition was reduced upon either saturation of the double bond in the side chain or cyclization to form the dihydrobenzofuran analogs [10].
  • Contrary to expectation, co-grafting of transfected GDNF-expressing HiB5 cells, a rat-derived neural cell line, tended to impair the survival of the grafts with the lowest values for graft volumes, TH-positive cell numbers, behavioral scores, and relative DOPA decarboxylase activity [11].
  • These results suggest that cAMP and protein kinase C mediate the PACAP-induced TH and DBH gene expression [12].
  • The membrane-associated form of TH (MTH) was activated by conditions favoring protein phosphorylation (e.g. ATP) and was inhibited by phosphatase (e.g. calf intestine phosphatase) [13].
  • A series of 1-phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes (1-phenyl-3-aminotetralins, PATs) previously was found to modulate tyrosine hydroxylase activity and dopamine synthesis in rodent forebrain through interaction with a binding site labeled by [(3)H]-(-)-(1R,3S)-trans-H(2)-PAT [14].

Anatomical context of TH


Associations of TH with chemical compounds

  • Leptin increased activating protein-1 DNA-binding activity, and this was diminished by Ro 32-0432 as well as EDTA, similar to the reduction of TH mRNA levels [20].
  • Nicardipine and omega-conotoxin GVIA, each at 1 microM, were effective at inhibiting leptin-induced TH enzyme activity, TH mRNA accumulation, PKC activity, and ERK activity [20].
  • However, these axons lacked IR for tyrosine hydroxylase (TH) and often ran in bundles with substance P (SP)-immunoreactive axons close to the epidermis [21].
  • 5-HT-containing cells (diam: 18.2 +/- 4.4 microns; n = 161) were smaller on average than both the NADPH-d (P < 0.01) and TH-containing cells (P < 0.01) [22].
  • Extrinsic nerves in the gallbladder that degenerated following chemical sympathectomy with 6-hydroxydopamine (6-OHDA), and which contained NPY, tyrosine hydroxylase (TH), and dopamine-beta-hydroxylase (DBH) immunoreactivities, formed a perivascular plexus closely associated with blood vessels [23].

Regulatory relationships of TH

  • The present study also showed that H89 (a PKA inhibitor) moderately, but significantly, inhibited leptin-induced ERK and TH mRNA [20].
  • Extirpation of the uterus reduced the expression of TH and induced the expression of GAL in the neurons [24].

Other interactions of TH


Analytical, diagnostic and therapeutic context of TH

  • HPLC was used to assess concentrations of catecholamines and Western blot analysis to detect total TH levels [16].
  • NOS-containing neurons were identified with NADPH-diaphorase (NADPH-d) histochemistry, and monoamine-containing neurons were identified with tyrosine hydroxylase (TH) and serotonin (5-HT) immunocytochemistry [22].
  • These findings also suggest that a subset of pUCM cells can differentiate into TH-positive cells within 8 weeks after transplantation into the 6-OHDA lesioned rat brain [29].
  • Immunoreactivities for tyrosine hydroxylase (TH), gamma-aminobutyric acid (GABA) and, in some cases, glutamic acid decarboxylase (GAD) were detected by light and electron microscopy in axons projecting into the median eminence and pituitary gland of various mammals (rats, mice, guinea pigs, cats, rabbits and hares) [30].
  • Immunosuppression did not impart a greater recovery of [18F]fluorodopa uptake, nor were the number of TH-positive graft neurons or the volumes of the grafts increased in the immunosuppressed group [11].


  1. Peripheral neurons innervating the extrinsic smooth penile musculature of the pig: experimental study by retrograde transport and immunohistochemistry. Botti, M., Ragionieri, L., Bo Minelli, L., Gazza, F., Acone, F., Panu, R., Palmieri, G. Italian journal of anatomy and embryology = Archivio italiano di anatomia ed embriologia. (2006) [Pubmed]
  2. Effects of chronic progressive myocardial hypertrophy on indexes of cardiac autonomic innervation. Lindpaintner, K., Lund, D.D., Schmid, P.G. Circ. Res. (1987) [Pubmed]
  3. Activity of tyrosine hydroxylase in the striatum of newborn piglets in response to hypocapnic hypoxia. Tammela, O., Pastuszko, A., Lajevardi, N.S., Delivoria-Papadopoulos, M., Wilson, D.F. J. Neurochem. (1993) [Pubmed]
  4. Activation of tyrosine hydroxylase in striatum of newborn piglets in response to hypocapnic ischemia and recovery. Pastuszko, P., Wilson, D.F. Adv. Exp. Med. Biol. (1997) [Pubmed]
  5. Modification of T cell antinuclease idiotype expression by in vivo administration of anti-idiotype. Miller, G.G., Nadler, P.I., Hodes, R.J., Sachs, D.H. J. Exp. Med. (1982) [Pubmed]
  6. In vitro acetylcholine biosynthesis in normal and failing guinea pig hearts. Roskoski, R., Schmid, P.G., Mayer, H.E., Abboud, F.M. Circ. Res. (1975) [Pubmed]
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  8. Neuronal colocalization of peptides, catecholamines, and catecholamine-synthesizing enzymes in guinea pig paracervical ganglia. Morris, J.L., Gibbins, I.L. J. Neurosci. (1987) [Pubmed]
  9. Topography of NPY-, somatostatin-, and VIP-immunoreactive, neuronal subpopulations in the guinea pig celiac-superior mesenteric ganglion and their projection to the pylorus. Lindh, B., Hökfelt, T., Elfvin, L.G., Terenius, L., Fahrenkrug, J., Elde, R., Goldstein, M. J. Neurosci. (1986) [Pubmed]
  10. Aromatic amino acid hydroxylase inhibitors. 4. 3-Substituted alpha-methyltyrosines. el-Masry, A.H., el-Masry, E.E., Hare, L.E., Counsell, R.E. J. Med. Chem. (1975) [Pubmed]
  11. Quantitative [18F]fluorodopa/PET and histology of fetal mesencephalic dopaminergic grafts to the striatum of MPTP-poisoned minipigs. Dall, A.M., Danielsen, E.H., Sørensen, J.C., Andersen, F., Møller, A., Zimmer, J., Gjedde, A.H., Cumming, P. Cell transplantation. (2002) [Pubmed]
  12. Pituitary adenylate cyclase-activating polypeptide induces gene expression of the catecholamine synthesizing enzymes, tyrosine hydroxylase and dopamine beta hydroxylase, through 3',5'-cyclic adenosine monophosphate- and protein kinase C-dependent mechanisms in cultured porcine adrenal medullary chromaffin cells. Isobe, K., Yukimasa, N., Nakai, T., Takuwa, Y. Neuropeptides (1996) [Pubmed]
  13. Demonstration of functional coupling between dopamine synthesis and its packaging into synaptic vesicles. Chen, R., Wei, J., Fowler, S.C., Wu, J.Y. J. Biomed. Sci. (2003) [Pubmed]
  14. Synthesis, evaluation, and comparative molecular field analysis of 1-phenyl-3-amino-1,2,3,4-tetrahydronaphthalenes as ligands for histamine H(1) receptors. Bucholtz, E.C., Brown, R.L., Tropsha, A., Booth, R.G., Wyrick, S.D. J. Med. Chem. (1999) [Pubmed]
  15. Immunohistochemical studies on the coexistence of catecholamine-synthesizing enzymes and neuropeptide Y in nerve fibers of the porcine pineal gland. Kaleczyc, J., Przybylska, B., Majewski, M., Lewczuk, B. J. Pineal Res. (1994) [Pubmed]
  16. Chronic placental insufficiency affects retinal development in the guinea pig. Loeliger, M., Briscoe, T., Lambert, G., Caddy, J., Rehn, A., Dieni, S., Rees, S. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
  17. Regional differences in the sympathetic innervation of the guinea pig large intestine by neuropeptide Y- and tyrosine hydroxylase-immunoreactive nerves of divergent extrinsic origin. Browning, K.N., Cunningham, S.M., Duncan, L., Timmermans, J., Lees, G.M. J. Comp. Neurol. (1999) [Pubmed]
  18. Regional distribution and extrinsic innervation of intrinsic cardiac neurons in the guinea pig. Leger, J., Croll, R.P., Smith, F.M. J. Comp. Neurol. (1999) [Pubmed]
  19. Tyrosine hydroxylase and acetylcholinesterase in the domestic pig mesencephalon: an immunocytochemical and histochemical study. Ostergaard, K., Holm, I.E., Zimmer, J. J. Comp. Neurol. (1992) [Pubmed]
  20. Leptin stimulates catecholamine synthesis in a PKC-dependent manner in cultured porcine adrenal medullary chromaffin cells. Takekoshi, K., Ishii, K., Nanmoku, T., Shibuya, S., Kawakami, Y., Isobe, K., Nakai, T. Endocrinology (2001) [Pubmed]
  21. Neuropeptide Y immunoreactivity in cutaneous sympathetic and sensory neurons during development of the guinea pig. Morris, J.L., Anderson, R.L., Gibbins, I.L. J. Comp. Neurol. (2001) [Pubmed]
  22. Interdigitation of nitric oxide synthase-, tyrosine hydroxylase-, and serotonin-containing neurons in and around the laterodorsal and pedunculopontine tegmental nuclei of the guinea pig. Leonard, C.S., Kerman, I., Blaha, G., Taveras, E., Taylor, B. J. Comp. Neurol. (1995) [Pubmed]
  23. Structure, afferent innervation, and transmitter content of ganglia of the guinea pig gallbladder: relationship to the enteric nervous system. Mawe, G.M., Gershon, M.D. J. Comp. Neurol. (1989) [Pubmed]
  24. Changes in the expression of tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), galanin (GAL), vasoactive intestinal polypeptide (VIP) and substance P (SP) in the uterine cervix-projecting neurons located in the lumbar paravertebral ganglia of the pig. Wasowicz, K. Folia morphologica. (2003) [Pubmed]
  25. Galanin-, neuropeptide Y- and enkephalin-like immunoreactivities in catecholamine-storing paraganglia of the fetal guinea pig and newborn pig. Fried, G., Meister, B., Wikström, M., Terenius, L., Goldstein, M. Cell Tissue Res. (1989) [Pubmed]
  26. Progesterone receptor and dopamine synthesizing enzymes in hypothalamic neurons of the guinea pig: an immunohistochemical triple-label analysis. Lemoine, S., Leroy, D., Warembourg, M. J. Chem. Neuroanat. (2005) [Pubmed]
  27. An immunohistochemical study of the catecholamine synthesizing enzymes and neuropeptides in the female guinea-pig uterus and vagina. Mitchell, B.S., Ahmed, E. Histochem. J. (1992) [Pubmed]
  28. Effects of topical capsaicin on autonomic nerves in experimentally-induced nasal hypersensitivity. An immunocytochemical study. Kitajiri, M., Kubo, N., Ikeda, H., Sato, K., Kumazawa, T. Acta oto-laryngologica. Supplementum. (1993) [Pubmed]
  29. Transplantation of pig stem cells into rat brain: proliferation during the first 8 weeks. Medicetty, S., Bledsoe, A.R., Fahrenholtz, C.B., Troyer, D., Weiss, M.L. Exp. Neurol. (2004) [Pubmed]
  30. Systematic presence of GABA-immunoreactivity in the tubero-infundibular and tubero-hypophyseal dopaminergic axonal systems: an ultrastructural immunogold study on several mammals. Schimchowitsch, S., Vuillez, P., Tappaz, M.L., Klein, M.J., Stoeckel, M.E. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (1991) [Pubmed]
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