Trialkyltin Compounds Bind Retinoid X Receptor to Alter Human Placental Endocrine Functions

DOI PDF PubMed 被引用文献24件 オープンアクセス
  • Tsuyoshi Nakanishi
    Laboratory of Environmental Biochemistry (J.N., T.N.), Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871;
  • Jun-ichi Nishikawa
    Laboratory of Environmental Biochemistry (J.N., T.N.), Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka 565-0871;
  • Youhei Hiromori
    Department of Toxicology (T.N., Y.H., H.Y., M.K., S.T., J.I., M.W., S.I., N.I., K.T.), Suita, Osaka 565-0871;
  • Hideaki Yokoyama
    Department of Toxicology (T.N., Y.H., H.Y., M.K., S.T., J.I., M.W., S.I., N.I., K.T.), Suita, Osaka 565-0871;
  • Mihoko Koyanagi
    Department of Toxicology (T.N., Y.H., H.Y., M.K., S.T., J.I., M.W., S.I., N.I., K.T.), Suita, Osaka 565-0871;
  • Shinri Takasuga
    Department of Toxicology (T.N., Y.H., H.Y., M.K., S.T., J.I., M.W., S.I., N.I., K.T.), Suita, Osaka 565-0871;
  • Jun-ichi Ishizaki
    Department of Toxicology (T.N., Y.H., H.Y., M.K., S.T., J.I., M.W., S.I., N.I., K.T.), Suita, Osaka 565-0871;
  • Mai Watanabe
    Department of Toxicology (T.N., Y.H., H.Y., M.K., S.T., J.I., M.W., S.I., N.I., K.T.), Suita, Osaka 565-0871;
  • Shun-ichi Isa
    Department of Toxicology (T.N., Y.H., H.Y., M.K., S.T., J.I., M.W., S.I., N.I., K.T.), Suita, Osaka 565-0871;
  • Naoki Utoguchi
    Laboratory of Pharmaceutics (N.U.), School of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195;
  • Norio Itoh
    Department of Toxicology (T.N., Y.H., H.Y., M.K., S.T., J.I., M.W., S.I., N.I., K.T.), Suita, Osaka 565-0871;
  • Yutaka Kohno
    Development Division (Y.K.), Fujisawa Pharmaceutical Co., Ltd., Osaka 532-8514, Japan
  • Tsutomu Nishihara
    Department of Toxicology (T.N., Y.H., H.Y., M.K., S.T., J.I., M.W., S.I., N.I., K.T.), Suita, Osaka 565-0871;
  • Keiichi Tanaka
    Department of Toxicology (T.N., Y.H., H.Y., M.K., S.T., J.I., M.W., S.I., N.I., K.T.), Suita, Osaka 565-0871;

この論文をさがす

説明

<jats:title>Abstract</jats:title><jats:p>Retinoid X receptor (RXR) is a nuclear receptor that plays important and multiple roles in mammalian development and homeostasis. We previously reported that, in human choriocarcinoma cells, tributyltin chloride and triphenyltin hydroxide, which are typical environmental contaminants and cause masculinization in female mollusks, are potent stimulators of human chorionic gonadotropin production and aromatase activity, which play key endocrine functions in maintaining pregnancy and fetal development. However, the molecular mechanism through which these compounds stimulate these endocrine functions remains unclear. Our current study shows that trialkyltin compounds, including tributyltin chloride and triphenyltin hydroxide, function as RXR agonists. Trialkyltins directly bind to the ligand-binding domain of RXR with high affinity and function as transcriptional activators. Unlike the natural RXR ligand, 9-cis-retinoic acid, the activity of trialkyltins is RXR specific and does not activate the retinoic acid receptor pathway. In addition, trialkyltins activate RXR to stimulate the expression of a luciferase reporter gene containing the human placental promoter I.1 sequence of aromatase, suggesting that trialkyltins stimulate human placental endocrine functions through RXR-dependent signaling pathways. Therefore, our results suggest that activation of RXR may be a novel mechanism by which trialkyltins alter human endocrine functions.</jats:p>

収録刊行物

被引用文献 (24)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ