Herbicide atrazine activates SF-1 by direct affinity and concomitant co-activators recruitments to induce aromatase expression via promoter II

Wu Qiang Fan, Toshihiko Yanase, Hidetaka Morinaga, Shigeki Gondo, Taijiro Okabe, Masatoshi Nomura, Tyrone B. Hayes, Ryoichi Takayanagi, Hajime Nawata

Research output: Contribution to journalArticlepeer-review

57 Citations (Scopus)

Abstract

The popular herbicide atrazine is an endocrine disruptor that demasculinizes and feminizes several species of animals, and co-relates with breast and reproductive disorders in mammalians. We recently reported that atrazine induces human aromatase gene expression via promoter II (ArPII) in a steroidogenic factor 1 (SF-1)-dependent manner. Here, we show that knockdown of SF-1 abolishes ArPII induction by atrazine in H295R cells, which harbor high SF-1 expression and are originally atrazine-responsive. Conversely, exogenous SF-1 enables atrazine to induce ArPII in the otherwise non-responsive KGN cells. Atrazine's effect is independent from protein kinase A and LRH-1, a close relative of SF-1. However, it binds directly to the SF-1, and concomitantly, enhances interactions of SF-1 with co-activator TIF2, and renders more SF-1 binding to ArPII chromatin. Intriguingly, LBD mutations do not alter SF-1's ability to mediate atrazine stimulation, suggesting that atrazine interacts with SF-1 via a region(s) other than the ligand binding pocket. These data suggest that atrazine binds to and activates SF-1 to induce ArPII.

Original languageEnglish
Pages (from-to)1012-1018
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume355
Issue number4
DOIs
Publication statusPublished - Apr 20 2007

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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