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Intrinsic Function of the Aryl Hydrocarbon (Dioxin) Receptor as a Key Factor in Female Reproduction
Open accessAbstract
Dioxins exert a variety of adverse effects on organisms, including teratogenesis, immunosuppression, tumor promotion, and estrogenic action. Studies using aryl hydrocarbon receptor (AhR)-deficient mice suggest that the majority of these toxic effects are mediated by the AhR. In spite of the adverse effects mediated by this receptor, the AhR gene is conserved among a number of animal species, ranging from invertebrates to vertebrates. This high degree of conservation strongly suggests that AhR possesses an important physiologic function, and a critical function is also supported by the reduced fertility observed with AhR-null female mice. We demonstrate that AhR plays a crucial role in female reproduction by regulating the expression of ovarian P450 aromatase (Cyp19), a key enzyme in estrogen synthesis. As revealed by in vitro reporter gene assay and in vivo chromatin immunoprecipitation assay, AhR cooperates with an orphan nuclear receptor, Ad4BP/SF-1, to activate Cyp19 gene transcription in ovarian granulosa cells. Administration to female mice of an AhR ligand, DMBA (9,10-dimethyl-1,2-benzanthracene), induced ovarian Cyp19 gene expression, irrespective of the intrinsic phase of the estrus cycle. In addition to elucidating a physiological function for AhR, our studies also suggest a possible mechanism for the toxic effects of exogenous AhR ligands as endocrine disruptors.
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“This mouse has also been used to examine fertility endpoints such that females were reported to be sub-fertile due to impaired follicular development and ovulation (Baba et al., 2005).”
From Rodent Genetic Models of Ah Receptor Signaling (2021) · cites this paper as Baba et al., 2005
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Cites
Poland, A., & Knutson, J. C. (1982) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.22.040182.002505 · Cited by 2,515
Denison, M. S., & Nagy, S. R. (2003) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.43.100901.135828 · Cited by 1,895
The Aryl Hydrocarbon Receptor Complex
Hankinson, O. (1995) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pa.35.040195.001515 · Cited by 1,649 · cited 1×
“A number of genes encoding drug-metabolizing enzymes, including CYP1A1 and genes encoding UDP-glucuronosyl transferase and glutathione S-transferase, have been identified as targets of AhR (18, 21).”
BackgroundFero, M. L., Rivkin, M. J., Tasch, M., Porter, P. L., Carow, C. E., Firpo, E. J., Polyák, K., Tsai, L., Broudy, V. C., Perlmutter, R. M., et al. (1996) · Cell · doi:10.1016/s0092-8674(00)81239-8 · Cited by 1,459
Poland, A., Glover, E., & Kende, A. S. (1976) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)33205-2 · Cited by 1,370
Enhanced Growth of Mice Lacking the Cyclin-Dependent Kinase Inhibitor Function of p27
Kiyokawa, H., Kineman, R. D., Manova-Todorova, K. O., Soares, V., Hoffman, E. S., Ono, M., Khanam, D., Hayday, A., Frohman, L. A., & Koff, A. (1996) · Cell · doi:10.1016/s0092-8674(00)81238-6 · Cited by 1,243
Dupont, S., Krust, A., Gansmuller, A., Dierich, A., Chambon, P., & Mark, M. (2000) · Development · doi:10.1242/dev.127.19.4277 · Cited by 1,064
Fisher, C. R., Graves, K. H., Parlow, A. F., & Simpson, E. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.12.6965 · Cited by 867
Hormonal Control of Gene Expression in the Ovary
Richards, J. S. (1994) · Endocrine Reviews · doi:10.1210/edrv-15-6-725 · Cited by 862
Modulation of oestrogen receptor signalling by association with the activated dioxin receptor
Ohtake, F., Takeyama, K., Μatsumoto, T., Kitagawa, H., Yamamoto, Y., Nohara, K., Tohyama, C., Krust, A., Mimura, J., Chambon, P., et al. (2003) · Nature · doi:10.1038/nature01606 · Cited by 798
Self-citationFunctional role of AhR in the expression of toxic effects by TCDD
Mimura, J., & Fujii‐Kuriyama, Y. (2003) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(02)00485-3 · Cited by 754
Self-citationAryl hydrocarbon receptors: diversity and evolution
Hahn, M. E. (2002) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(02)00070-4 · Cited by 642
Benzo[ a ]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor
Shimizu, Y., Nakatsuru, Y., Ichinose, M., Takahashi, Y., Kume, H., Mimura, J., Fujii‐Kuriyama, Y., & Ishikawa, T. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.2.779 · Cited by 640
Self-citationMimura, J., Yamashita, K., Nakamura, K., Morita, M., Takagi, T. N., Nakao, K., Ema, M., Sogawa, K., Yasuda, M., Katsuki, M., et al. (1997) · Genes to Cells · doi:10.1046/j.1365-2443.1997.1490345.x · Cited by 626
Self-citationAnalysis of Chromatin Structure byin VivoFormaldehyde Cross-Linking
Orlando, V., Strutt, H. L., & Paro, R. (1997) · Methods · doi:10.1006/meth.1996.0407 · Cited by 607
Identification of a novel mechanism of regulation of Ah (dioxin) receptor functionPreprint
Mimura, J., Ema, M., Sogawa, K., & Fujii‐Kuriyama, Y. (1999) · Genes & Development · doi:10.1101/gad.13.1.20 · Cited by 602
Self-citationA common trans-acting factor, Ad4-binding protein, to the promoters of steroidogenic P-450s.
Morohashi, K.-I., Honda, S., Inomata, Y., Handa, H., & Omura, T. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)37129-7 · Cited by 537
Self-citationNelson, J. F., Felicio, L. S., Randall, P. K., Sims, C., & Finch, C. E. (1982) · Biology of Reproduction · doi:10.1095/biolreprod27.2.327 · Cited by 523
Meyer, B., Pray-Grant, M. G., Heuvel, J. P. V., & Perdew, G. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.2.978 · Cited by 390
An essential role for C/EBPβ in female reproductionPreprint
Sterneck, E., Tessarollo, L., & Johnson, P. F. (1997) · Genes & Development · doi:10.1101/gad.11.17.2153 · Cited by 387
Harada, N., Utsumi, T., & Takagi, Y. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.11312 · Cited by 361
Self-citationFujisawa‐Sehara, A., Sogawa, K., Yamane, M., & Fujii‐Kuriyama, Y. (1987) · Nucleic Acids Research · doi:10.1093/nar/15.10.4179 · Cited by 313
Self-citationKazlauskas, A., Poellinger, L., & Pongratz, I. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.19.13519 · Cited by 302
Lowrey, P. L., & Takahashi, J. S. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.533 · Cited by 296
Callard, G. V., Tchoudakova, A., Kishida, M., & Wood, E. (2001) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(01)00147-9 · Cited by 296
Synergy between LRH-1 and β-Catenin Induces G1 Cyclin-Mediated Cell Proliferation
Botrugno, O. A., Fayard, E., Annicotte, J., Haby, C., Brennan, T., Wendling, O., Tanaka, T., Kodama, T., Thomas, W., Auwerx, J. H., et al. (2004) · Molecular Cell · doi:10.1016/j.molcel.2004.07.009 · Cited by 270
Lynch, J. P., Lala, D. S., Peluso, J. J., Luo, W., Parker, K. L., & White, B. A. (1993) · Molecular Endocrinology · doi:10.1210/mend.7.6.8395654 · Cited by 266
Means, G. D., Kilgore, M. W., Mahendroo, M. S., Mendelson, C. R., & Simpson, E. R. (1991) · Molecular Endocrinology · doi:10.1210/mend-5-12-2005 · Cited by 258
Virus Infection Leads to Localized Hyperacetylation of Histones H3 and H4 at the IFN-β Promoter
Parekh, B. S., & Maniatis, T. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80181-1 · Cited by 255
Perspective: The Ovarian Follicle--A Perspective in 2001
Richards, J. S. (2001) · Endocrinology · doi:10.1210/endo.142.6.8223 · Cited by 243
Liver Receptor Homologue-1 (LRH-1) Regulates Expression of Aromatase in Preadipocytes
Clyne, C. D., Speed, C. J., Zhou, J., & Simpson, E. R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201117200 · Cited by 233
Meyer, B. K., & Perdew, G. H. (1999) · Biochemistry · doi:10.1021/bi982223w · Cited by 232
Adverse Reproductive Outcomes in the Transgenic Ah Receptor-Deficient Mouse
Abbott, B. D., Schmid, J. E., Pitt, J. A., Buckalew, A. R., Wood, C. R., Held, G. A., & Diliberto, J. J. (1999) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1998.8601 · Cited by 219
Carlone, D. L., & Richards, J. S. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.3.9900 · Cited by 218
Morohashi, K., Zanger, U. M., Honda, S., Hara, M., Waterman, M. R., & Omura, T. (1993) · Molecular Endocrinology · doi:10.1210/mend.7.9.8247022 · Cited by 217
Self-citationPhysiological Role of the Aryl Hydrocarbon Receptor in Mouse Ovary Development
Benedict, J. C. (2000) · Toxicological Sciences · doi:10.1093/toxsci/56.2.382 · Cited by 211
Sebastian, S., & Bulun, S. E. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.10.7947 · Cited by 198
Structure and Expression of the Ah Receptor Repressor Gene
Baba, T., Mimura, J., Gradin, K., Kuroiwa, A., Watanabe, T., Matsuda, Y., Inazawa, J., Sogawa, K., & Fujii‐Kuriyama, Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011497200 · Cited by 192
Self-citationWhitelaw, M. L., Pongratz, I., Wilhelmsson, A., Gustafsson, J.-Å., & Poellinger, L. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.4.2504 · Cited by 191
Tchoudakova, A., Kishida, M., Wood, E., & Callard, G. V. (2001) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(01)00120-0 · Cited by 183
Differential Expression of Steroidogenic Factor-1 and FTF/LRH-1 in the Rodent Ovary
Falender, A. E., Lanz, R. B., Malenfant, D., Bélanger, L., & Richards, J. S. (2003) · Endocrinology · doi:10.1210/en.2002-0137 · Cited by 166
Gene regulation of steroidogenesis
Omura, T., & Morohashi, K.-I. (1995) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/0960-0760(95)00036-y · Cited by 159
Self-citationRobles, R., Morita, Y., Mann, K. K., Perez, G. I., Yang, S., Matikainen, T., Sherr, D. H., & Tilly, J. L. (2000) · Endocrinology · doi:10.1210/endo.141.1.7374 · Cited by 156
Harada, N. (1988) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a122213 · Cited by 155
Self-citationPrenatal TCDD and predisposition to mammary cancer in the rat
Brown, N. (1998) · Carcinogenesis · doi:10.1093/carcin/19.9.1623 · Cited by 151
The 5′-Flanking Regions of CYP19A1 and CYP19A2 in Zebrafish
Kazeto, Y., Ijiri, S., Place, A. R., Zohar, Y., & Trant, J. M. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5796 · Cited by 150
Hinshelwood, M. M., Repa, J. J., Shelton, J. M., Richardson, J. A., Mangelsdorf, D. J., & Mendelson, C. R. (2003) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(03)00257-0 · Cited by 148
Mizusaki, H., Kawabe, K., Mukai, T., Ariyoshi, E., Kasahara, M., Yoshioka, H., Swain, A., & Morohashi, K.-I. (2003) · Molecular Endocrinology · doi:10.1210/me.2002-0362 · Cited by 140
Self-citationCell Density Regulates Intracellular Localization of Aryl Hydrocarbon Receptor
Ikuta, T., Kobayashi, Y., & Kawajiri, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m310492200 · Cited by 125
Gonadotropin releasing hormone stimulates calmodulin redistribution in rat pituitary
Conn, P. M., Chafouleas, J. G., ROGERS, D. C., & Means, A. R. (1981) · Nature · doi:10.1038/292264a0 · Cited by 117
Komatsu, T., Mizusaki, H., Mukai, T., Ogawa, H., Baba, D., Shirakawa, M., Hatakeyama, S., Nakayama, K. I., Yamamoto, H., Kikuchi, A., et al. (2004) · Molecular Endocrinology · doi:10.1210/me.2004-0173 · Cited by 113
Self-citationAnalysis of zebrafish cyp19 promoters
Tong, S., & Chung, B. (2003) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(03)00347-9 · Cited by 111
Hewitt, S. C., Goulding, E. H., Eddy, E. M., & Korach, K. S. (2002) · Biology of Reproduction · doi:10.1095/biolreprod67.4.1268 · Cited by 108
Ikuta, T., Kobayashi, Y., & Kawajiri, K. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.03.076 · Cited by 99
Benedict, J. C., Miller, K. P., Lin, T.-M., Greenfeld, C. R., Babus, J. K., Peterson, R. E., & Flaws, J. A. (2003) · Biology of Reproduction · doi:10.1095/biolreprod.102.007492 · Cited by 89
Regulation of aromatase expression by the nuclear receptor LRH-1 in adipose tissue
Clyne, C. D., Kovacic, A., Speed, C. J., Zhou, J., Pezzi, V., & Simpson, E. R. (2004) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2003.11.001 · Cited by 69
Pall, M., Hellberg, P., Brännström, M., Mikuni, M., Peterson, C. M., Sundfeldt, K., Nordén, B., Hedin, L., & Enerbäck, S. (1997) · The EMBO Journal · doi:10.1093/emboj/16.17.5273 · Cited by 57
Nomura, M., Kawabe, K., Matsushita, S., Oka, S., Hatano, O., Harada, N., Nawata, H., & Morohashi, K. (1998) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a022083 · Cited by 42
Self-citationGibbons, A. (1993) · Science · doi:10.1126/science.8248776 · Cited by 40
Roby, K. F. (2001) · Endocrinology · doi:10.1210/en.142.6.2328 · Cited by 37
YOSHINAGA-HIRABAYASHI, T., Ishimura, K., Fujita, H., Kitawaki, J., & Osawa, Y. (1990) · Histochemistry and Cell Biology · doi:10.1007/bf00266381 · Cited by 24
Stanislaus, D., Janovick, J. A., Ji, T. H., Wilkie, T. M., Offermanns, S., & Conn, P. M. (1998) · Endocrinology · doi:10.1210/endo.139.6.5942 · Cited by 22
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Beischlag, T. V., Morales, J. L., Hollingshead, B. D., & Perdew, G. H. (2008) · Critical Reviews™ in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v18.i3.20 · Cited by 727
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Ohtake, F., Baba, A., Takada, I., Okada, M., Iwasaki, K., Miki, H., Takahashi, S., Kouzmenko, A., Nohara, K., Chiba, T., et al. (2007) · Nature · doi:10.1038/nature05683 · Cited by 585
Self-citationBonefeld‐Jørgensen, E. C., Long, M., Hofmeister, M. V., & Vinggaard, A. M. (2007) · Environmental Health Perspectives · doi:10.1289/ehp.9368 · Cited by 504
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Metadata
- Authors
- Baba, T., Mimura, J., Nakamura, N., Harada, N., Yamamoto, M., Morohashi, K.-I., & Fujii-Kuriyama, Y.
- Affiliations
- National Institute for Basic Biology (JP)
- University of Tsukuba (JP)
- Fujita Health University (JP)
- TARA Center, University of Tsukuba, 1-1-1 Tennoudai
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2005-11
- Volume
- 25
- Issue
- 22
- Pages
- 10040-10051
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1280268
- OpenAlex
- W2142798058
- Cited by
- 256
- References
- 62
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 6 · 2023: 10 · 2022: 5 · 2021: 9 · 2020: 16 · 2019: 11 · 2018: 11 · 2017: 11 · 2016: 8 · 2015: 7 · 2014: 5 · 2013: 20 · 2012: 15
- FWCI
- 8.30
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Core Research for Evolutional Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- aryl hydrocarbon receptor, dioxins, female reproduction, aromatase, estrogen synthesis, granulosa cells, Ad4BP/SF-1, nuclear receptor transcriptional regulation, endocrine disruptors, 7,12-dimethylbenz(a)anthracene, fertility
- MeSH terms
- Animals, Aromatase, Estradiol, Estrogens, Female, Gene Expression Regulation, Genotype, Granulosa Cells, Humans, Immunohistochemistry, Ligands, Luciferases, Male, Models, Genetic, Ovary, Ovulation, Phenotype, Promoter Regions, Genetic, Reproduction, Steroids, Transcription Factors, Transcription, Genetic, Transfection, 9,10-Dimethyl-1,2-benzanthracene, Up-Regulation, Polymerase Chain Reaction, Genes, Reporter, DNA Primers, Receptors, Cytoplasmic and Nuclear, Receptors, Aryl Hydrocarbon, Homeodomain Proteins, Chromatin Immunoprecipitation, Immunoprecipitation, Mice, Steroidogenic Factor 1
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