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

研究成果: Article査読

198 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)10040-10051
ページ数12
ジャーナルMolecular and cellular biology
25
22
DOI
出版ステータスPublished - 2005 11月
外部発表はい

ASJC Scopus subject areas

  • 分子生物学
  • 細胞生物学

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