Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction

Takashi Baba, Junsei Mimura, Naohito Nakamura, Nobuhiro Harada, Masayuki Yamamoto, Ken-Ichirou Morohashi, Yoshiaki Fujii-Kuriyama

Research output: Contribution to journalArticle

168 Citations (Scopus)

Abstract

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 disrupters.

Original languageEnglish
Pages (from-to)10040-10051
Number of pages12
JournalMolecular and cellular biology
Volume25
Issue number22
DOIs
Publication statusPublished - Nov 1 2005

Fingerprint

Aryl Hydrocarbon Receptors
Reproduction
Poisons
Orphan Nuclear Receptors
Teratogenesis
Ligands
9,10-Dimethyl-1,2-benzanthracene
Dioxins
Aromatase
Granulosa Cells
Chromatin Immunoprecipitation
Estrus
Invertebrates
Reporter Genes
Immunosuppression
Genes
Fertility
Vertebrates
Estrogens
Gene Expression

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction. / Baba, Takashi; Mimura, Junsei; Nakamura, Naohito; Harada, Nobuhiro; Yamamoto, Masayuki; Morohashi, Ken-Ichirou; Fujii-Kuriyama, Yoshiaki.

In: Molecular and cellular biology, Vol. 25, No. 22, 01.11.2005, p. 10040-10051.

Research output: Contribution to journalArticle

Baba, Takashi ; Mimura, Junsei ; Nakamura, Naohito ; Harada, Nobuhiro ; Yamamoto, Masayuki ; Morohashi, Ken-Ichirou ; Fujii-Kuriyama, Yoshiaki. / Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction. In: Molecular and cellular biology. 2005 ; Vol. 25, No. 22. pp. 10040-10051.
@article{40793df387724afabbac0a1cafc2f798,
title = "Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction",
abstract = "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 disrupters.",
author = "Takashi Baba and Junsei Mimura and Naohito Nakamura and Nobuhiro Harada and Masayuki Yamamoto and Ken-Ichirou Morohashi and Yoshiaki Fujii-Kuriyama",
year = "2005",
month = "11",
day = "1",
doi = "10.1128/MCB.25.22.10040-10051.2005",
language = "English",
volume = "25",
pages = "10040--10051",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "22",

}

TY - JOUR

T1 - Intrinsic function of the aryl hydrocarbon (dioxin) receptor as a key factor in female reproduction

AU - Baba, Takashi

AU - Mimura, Junsei

AU - Nakamura, Naohito

AU - Harada, Nobuhiro

AU - Yamamoto, Masayuki

AU - Morohashi, Ken-Ichirou

AU - Fujii-Kuriyama, Yoshiaki

PY - 2005/11/1

Y1 - 2005/11/1

N2 - 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 disrupters.

AB - 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 disrupters.

UR - http://www.scopus.com/inward/record.url?scp=27644564007&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27644564007&partnerID=8YFLogxK

U2 - 10.1128/MCB.25.22.10040-10051.2005

DO - 10.1128/MCB.25.22.10040-10051.2005

M3 - Article

VL - 25

SP - 10040

EP - 10051

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 22

ER -