Tributyltin or triphenyltin inhibits aromatase activity in the human granulosa-like tumor cell line KGN

Masayuki Saitoh, Toshihiko Yanase, Hidetaka Morinaga, Makito Tanabe, Yi Ming Mu, Yoshihiro Nishi, Masatoshi Nomura, Taijiro Okabe, Kiminobu Goto, Ryoichi Takayanagi, Hajime Nawata

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Abstract

The superimposition of male sex organs (penis and vas deferens) in a female gastropod, called imposex, is widely attributed to the exposure to tributyltin (TBT) compounds, used world-wide in antifouling paints for ships. It has been hypothesized that the TBT-induced imposex is mediated by an increasing androgen level relative to the estrogen level, namely a decreased conversion of androgens to estrogens (i.e., aromatization). In the present study, we tested this hypothesis by examining the effects of TBT or triphenyltin (TPT) on the aromatase activity in a cultured human granulosa-like tumor cell line, KGN, which was recently established by our group. Treatment with more than 1000 ng/ml TBT compounds was very toxic to the cells and caused immediate cell death within 24 h, while 200 ng/ml was found to cause apoptosis of the cells. Treatment of the KGN cells for more than 48 h with 20 ng/ml TBT or TPT, which is a concentration level reported to cause imposex in marine species, did not affect cell proliferation but significantly suppressed the aromatase activity determined by a [3H]H2O release assay. Treatment with 20 ng/ml TBT compounds for 7 days also resulted in a reduction of the E2 production from Δ4-androstenedione stimulated by db-cAMP. The changes in the aromatase activity by TBT compounds were associated with comparable changes in P450arom mRNA assessed by RT-PCR. The luciferase activity of the P450arom promoter II (1 kb) decreased after the addition of 20 ng/ml TBT compounds in transfected KGN cells either in a basic state or in states stimulated by db-cAMP. The Ad4BP-dependent increase in the luciferase activity of P450arom promoter II was also downregulated by such treatments. These results indicate that TBT compounds inhibited the aromatase activity and also decreased the P450arom mRNA level at the transcriptional level in KGN cells. The direct inhibitory effect of TBT compounds on the aromatase activity may therefore partly explain the induction of imposex by these compounds in female species.

Original languageEnglish
Pages (from-to)198-204
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume289
Issue number1
DOIs
Publication statusPublished - Nov 23 2001

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Aromatase
Tumor Cell Line
Human Activities
Tumors
Cells
Luciferases
Androgens
Estrogens
Antifouling paint
tributyltin
triphenyltin
Aromatization
Messenger RNA
Gastropoda
Paint
Vas Deferens
Ships
Androstenedione
Poisons
Penis

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Tributyltin or triphenyltin inhibits aromatase activity in the human granulosa-like tumor cell line KGN. / Saitoh, Masayuki; Yanase, Toshihiko; Morinaga, Hidetaka; Tanabe, Makito; Mu, Yi Ming; Nishi, Yoshihiro; Nomura, Masatoshi; Okabe, Taijiro; Goto, Kiminobu; Takayanagi, Ryoichi; Nawata, Hajime.

In: Biochemical and Biophysical Research Communications, Vol. 289, No. 1, 23.11.2001, p. 198-204.

Research output: Contribution to journalArticle

Saitoh, M, Yanase, T, Morinaga, H, Tanabe, M, Mu, YM, Nishi, Y, Nomura, M, Okabe, T, Goto, K, Takayanagi, R & Nawata, H 2001, 'Tributyltin or triphenyltin inhibits aromatase activity in the human granulosa-like tumor cell line KGN', Biochemical and Biophysical Research Communications, vol. 289, no. 1, pp. 198-204. https://doi.org/10.1006/bbrc.2001.5952
Saitoh, Masayuki ; Yanase, Toshihiko ; Morinaga, Hidetaka ; Tanabe, Makito ; Mu, Yi Ming ; Nishi, Yoshihiro ; Nomura, Masatoshi ; Okabe, Taijiro ; Goto, Kiminobu ; Takayanagi, Ryoichi ; Nawata, Hajime. / Tributyltin or triphenyltin inhibits aromatase activity in the human granulosa-like tumor cell line KGN. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 289, No. 1. pp. 198-204.
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