The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Ahr  -  aryl hydrocarbon receptor

Rattus norvegicus

Synonyms: Ah receptor, AhR, Aryl hydrocarbon receptor
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Ahr


High impact information on Ahr

  • The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that is best known because it mediates the actions of polycyclic and halogenated aromatic hydrocarbon environmental toxicants such as 3-methylcholanthrene and 2,3,7,8-tetrachlorodibenzo-p-dioxin [6].
  • In a reporter gene assay, this ligand activates the AHR with a potency five times greater than that of beta-naphthoflavone, a prototypical synthetic AHR ligand [6].
  • 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester competes with 2,3,7,8-[(3)H]tetrachlorodibenzo-p-dioxin for binding to human, murine, and fish AHRs, thus showing that AHR activation is caused by direct receptor binding, and that recognition of this endogenous ligand is conserved from early vertebrates (fish) to humans [6].
  • Down-regulation of nuclear aryl hydrocarbon receptor DNA-binding and transactivation functions: requirement for a labile or inducible factor [7].
  • H/W rats are exceptionally resistant to induction of AHF by TCDD, and the resistance is associated with an altered transactivation domain of the aryl hydrocarbon receptor [8].

Chemical compound and disease context of Ahr

  • We have investigated mechanisms of omeprazole (OME)-mediated induction of CYP1A1 and CYP3A, using the rat hepatoma H4IIE cell line, in comparison with mechanisms exerted by traditional aryl hydrocarbon receptor (AhR) ligands such as benso(a)pyrene (B(a)P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) [1].
  • The dependency of the cytostatic effects of five flavonoids (flavone, alpha-naphthoflavone, apigenin, 3'-methoxy-4'-nitroflavone and 2'-amino-3'-methoxyflavone) on a functional AHR was examined in AHR-containing rat hepatoma 5L cells and an AHR-deficient cell line (BP8) derived from the 5L line [9].
  • Sucrose gradient analyses using rat liver and murine hepatoma 1c1c7 extracts demonstrated that SP600125 competed with TCDD for binding to the AhR [10].
  • Thus, DIM represents a new class of relatively non-toxic AhR-based antiestrogens that inhibit E2-dependent tumor growth in rodents and current studies are focused on development of analogs for clinical treatment of breast cancer [11].
  • Coordinate responses of UGT activity after treatment with TCDD or tBHQ were also observed in rat hepatoma 5L cells, mutants without the AhR and with recomplemented AhR [12].

Biological context of Ahr


Anatomical context of Ahr


Associations of Ahr with chemical compounds

  • Northern blotting demonstrated that, in the mediobasal hypothalamus, a subcutaneous injection of 20 microg estradiol benzoate (E(2)) significantly increased the expression of Arnt2 mRNA, but induced no significant changes in the expression of AhR and Arnt1 mRNAs [20].
  • By using a compendium of gene expression profiles, FLU was shown to signal in rats similar to an AhR activator with additional CYP2B and CYP3A effects that most resembled the ADME gene expression pattern of the atypical CYP1A inducers I3C and OME [21].
  • This preliminary report is the first study to suggest that the PAS proteins, AhR and Arnt, exhibit a daily oscillation pattern within multiple target tissues which may give insight into the tissue-specific toxic and biochemical responses mediated through this dimerization pair, as well as the physiological function of these proteins [16].
  • These results suggest that the transient decreases in androgen-regulated prostatic mRNA abundance observed in response to in utero and lactational TCDD exposure were probably not the result of direct action of the activated AhR on these genes but instead were reflective of a TCDD-induced delay in prostate development [22].
  • Profiling the hepatic effects of flutamide in rats: a microarray comparison with classical aryl hydrocarbon receptor ligands and atypical CYP1A inducers [21].

Physical interactions of Ahr


Co-localisations of Ahr

  • There was no neuroanatomic evidence that AhR is preferentially colocalized with ARNT or ARNT2 [25].

Regulatory relationships of Ahr


Other interactions of Ahr

  • Gel shift analysis with radiolabeled XRE and specific peptide antibodies toward AhR and aryl hydrocarbon receptor nuclear translocator protein (Arnt) revealed an OME-mediated translocation of the AhR.Arnt complex into the nuclei [1].
  • Assessment of metabolites and AhR and CYP1A1 mRNA expression subsequent to prenatal exposure to inhaled benzo(a)pyrene [2].
  • These results suggest that both AhR and Nrf2 pathways are active in WAT and that lipophilic compounds accumulated in WAT can activate these transcription factors to increase detoxification capability in the tissue [19].
  • Independent observations demonstrated that AhR-mediated G(1) phase cell cycle arrest depends on an interaction with the retinoblastoma tumor suppressor protein (pRb), but differences exist regarding proposed mechanisms of action [13].
  • Also in the latter, in the vacuolated acinar cells, CYP1A1 was overexpressed, and statistically significant decreases in expressions of AhR, CCKAR, and amylase occurred [29].

Analytical, diagnostic and therapeutic context of Ahr


  1. Signal transduction-mediated activation of the aryl hydrocarbon receptor in rat hepatoma H4IIE cells. Backlund, M., Johansson, I., Mkrtchian, S., Ingelman-Sundberg, M. J. Biol. Chem. (1997) [Pubmed]
  2. Assessment of metabolites and AhR and CYP1A1 mRNA expression subsequent to prenatal exposure to inhaled benzo(a)pyrene. Wu, J., Ramesh, A., Nayyar, T., Hood, D.B. Int. J. Dev. Neurosci. (2003) [Pubmed]
  3. CYP1 and AhR expression in 7,12-dimethylbenz[a]anthracene-induced mammary carcinoma of rats prenatally exposed to 3,3',4,4',5-pentachlorobiphenyl. Wakui, S., Yokoo, K., Takahashi, H., Muto, T., Suzuki, Y., Kanai, Y., Hano, H., Furusato, M., Endou, H. Toxicology (2005) [Pubmed]
  4. In vitro inhibition of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced activity by alpha-naphthoflavone and 6-methyl-1,3,8-trichlorodibenzofuran using an aryl hydrocarbon (Ah)-responsive construct. Merchant, M., Safe, S. Biochem. Pharmacol. (1995) [Pubmed]
  5. Identification of 3'-methoxy-4'-nitroflavone as a pure aryl hydrocarbon (Ah) receptor antagonist and evidence for more than one form of the nuclear Ah receptor in MCF-7 human breast cancer cells. Lu, Y.F., Santostefano, M., Cunningham, B.D., Threadgill, M.D., Safe, S. Arch. Biochem. Biophys. (1995) [Pubmed]
  6. A ligand for the aryl hydrocarbon receptor isolated from lung. Song, J., Clagett-Dame, M., Peterson, R.E., Hahn, M.E., Westler, W.M., Sicinski, R.R., DeLuca, H.F. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  7. Down-regulation of nuclear aryl hydrocarbon receptor DNA-binding and transactivation functions: requirement for a labile or inducible factor. Reick, M., Robertson, R.W., Pasco, D.S., Fagan, J.B. Mol. Cell. Biol. (1994) [Pubmed]
  8. Liver tumor-promoting activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in TCDD-sensitive and TCDD-resistant rat strains. Viluksela, M., Bager, Y., Tuomisto, J.T., Scheu, G., Unkila, M., Pohjanvirta, R., Flodström, S., Kosma, V.M., Mäki-Paakkanen, J., Vartiainen, T., Klimm, C., Schramm, K.W., Wärngård, L., Tuomisto, J. Cancer Res. (2000) [Pubmed]
  9. Suppression of cell cycle progression by flavonoids: dependence on the aryl hydrocarbon receptor. Reiners, J.J., Clift, R., Mathieu, P. Carcinogenesis (1999) [Pubmed]
  10. The Jun N-terminal kinase inhibitor SP600125 is a ligand and antagonist of the aryl hydrocarbon receptor. Joiakim, A., Mathieu, P.A., Palermo, C., Gasiewicz, T.A., Reiners, J.J. Drug Metab. Dispos. (2003) [Pubmed]
  11. Aryl hydrocarbon receptor-mediated antiestrogenic and antitumorigenic activity of diindolylmethane. Chen, I., McDougal, A., Wang, F., Safe, S. Carcinogenesis (1998) [Pubmed]
  12. Contribution of the Ah receptor to the phenolic antioxidant-mediated expression of human and rat UDP-glucuronosyltransferase UGT1A6 in Caco-2 and rat hepatoma 5L cells. Münzel, P.A., Schmohl, S., Buckler, F., Jaehrling, J., Raschko, F.T., Köhle, C., Bock, K.W. Biochem. Pharmacol. (2003) [Pubmed]
  13. Multiple mechanisms are involved in Ah receptor-mediated cell cycle arrest. Huang, G., Elferink, C.J. Mol. Pharmacol. (2005) [Pubmed]
  14. Reduction in 7,12-Dimethylbenz[a]anthracene-Induced Hepatic Cytochrome-P450 1A1 Expression Following Soy Consumption in Female Rats Is Mediated by Degradation of the Aryl Hydrocarbon Receptor. Singhal, R., Badger, T.M., Ronis, M.J. J. Nutr. (2007) [Pubmed]
  15. Strain differences in cytochrome P4501A1 gene expression caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat liver: role of the aryl hydrocarbon receptor and its nuclear translocator. Jana, N.R., Sarkar, S., Yonemoto, J., Tohyama, C., Sone, H. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  16. Daily cycle of bHLH-PAS proteins, Ah receptor and Arnt, in multiple tissues of female Sprague-Dawley rats. Richardson, V.M., Santostefano, M.J., Birnbaum, L.S. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  17. Linked expression of Ah receptor, ARNT, CYP1A1, and CYP1B1 in rat mammary epithelia, in vitro, is each substantially elevated by specific extracellular matrix interactions that precede branching morphogenesis. Larsen, M.C., Brake, P.B., Pollenz, R.S., Jefcoate, C.R. Toxicol. Sci. (2004) [Pubmed]
  18. Responsiveness of the adult male rat reproductive tract to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: Ah receptor and ARNT expression, CYP1A1 induction, and Ah receptor down-regulation. Roman, B.L., Pollenz, R.S., Peterson, R.E. Toxicol. Appl. Pharmacol. (1998) [Pubmed]
  19. Induction of detoxifying enzymes in rodent white adipose tissue by aryl hydrocarbon receptor agonists and antioxidants. Yoshinari, K., Okino, N., Sato, T., Sugatani, J., Miwa, M. Drug Metab. Dispos. (2006) [Pubmed]
  20. Estrogen increases messenger RNA and immunoreactivity of aryl-hydrocarbon receptor nuclear translocator 2 in the rat mediobasal hypothalamus. Mitsushima, D., Funabashi, T., Kimura, F. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  21. Profiling the hepatic effects of flutamide in rats: a microarray comparison with classical aryl hydrocarbon receptor ligands and atypical CYP1A inducers. Coe, K.J., Nelson, S.D., Ulrich, R.G., He, Y., Dai, X., Cheng, O., Caguyong, M., Roberts, C.J., Slatter, J.G. Drug Metab. Dispos. (2006) [Pubmed]
  22. In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs prostate development. 1. Effects on gene expression. Roman, B.L., Peterson, R.E. Toxicol. Appl. Pharmacol. (1998) [Pubmed]
  23. Regulation of CYP1A1 transcription via the metabolism of the tryptophan-derived 6-formylindolo[3,2-b]carbazole. Wei, Y.D., Bergander, L., Rannug, U., Rannug, A. Arch. Biochem. Biophys. (2000) [Pubmed]
  24. Maximal aryl hydrocarbon receptor activity depends on an interaction with the retinoblastoma protein. Elferink, C.J., Ge, N.L., Levine, A. Mol. Pharmacol. (2001) [Pubmed]
  25. Distribution of mRNAs encoding the arylhydrocarbon receptor, arylhydrocarbon receptor nuclear translocator, and arylhydrocarbon receptor nuclear translocator-2 in the rat brain and brainstem. Petersen, S.L., Curran, M.A., Marconi, S.A., Carpenter, C.D., Lubbers, L.S., McAbee, M.D. J. Comp. Neurol. (2000) [Pubmed]
  26. Characterization of in vitro metabolites of the aryl hydrocarbon receptor ligand 6-formylindolo[3,2-b]carbazole by liquid chromatography-mass spectrometry and NMR. Bergander, L., Wahlström, N., Alsberg, T., Bergman, J., Rannug, A., Rannug, U. Drug Metab. Dispos. (2003) [Pubmed]
  27. Alteration in ovarian gene expression in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin: reduction of cyclooxygenase-2 in the blockage of ovulation. Mizuyachi, K., Son, D.S., Rozman, K.K., Terranova, P.F. Reprod. Toxicol. (2002) [Pubmed]
  28. Binding of aromatic amines to the rat hepatic Ah receptor in vitro and in vivo and to the 8S and 4S estrogen receptor of rat uterus and rat liver. Cikryt, P., Kaiser, T., Göttlicher, M. Environ. Health Perspect. (1990) [Pubmed]
  29. Mechanisms of exocrine pancreatic toxicity induced by oral treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin in female Harlan Sprague-Dawley Rats. Yoshizawa, K., Marsh, T., Foley, J.F., Cai, B., Peddada, S., Walker, N.J., Nyska, A. Toxicol. Sci. (2005) [Pubmed]
  30. Interactions of polybrominated diphenyl ethers with the aryl hydrocarbon receptor pathway. Peters, A.K., Nijmeijer, S., Gradin, K., Backlund, M., Bergman, A., Poellinger, L., Denison, M.S., Van den Berg, M. Toxicol. Sci. (2006) [Pubmed]
  31. A novel computational approach for the prediction of networked transcription factors of aryl hydrocarbon-receptor-regulated genes. Kel, A., Reymann, S., Matys, V., Nettesheim, P., Wingender, E., Borlak, J. Mol. Pharmacol. (2004) [Pubmed]
  32. Point mutation in intron sequence causes altered carboxyl-terminal structure in the aryl hydrocarbon receptor of the most 2,3,7,8-tetrachlorodibenzo-p-dioxin-resistant rat strain. Pohjanvirta, R., Wong, J.M., Li, W., Harper, P.A., Tuomisto, J., Okey, A.B. Mol. Pharmacol. (1998) [Pubmed]
  33. In vivo up-regulation of aryl hydrocarbon receptor expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in a dioxin-resistant rat model. Franc, M.A., Pohjanvirta, R., Tuomisto, J., Okey, A.B. Biochem. Pharmacol. (2001) [Pubmed]
WikiGenes - Universities