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(In Japanese)低用量ダイオキシン類による内分泌かく乱作用

Research report code R013000250
Posted date Oct 1, 2003
  • (In Japanese)遠山 千春
  • (In Japanese)国立環境研究所
Research organization
  • (In Japanese)国立環境研究所
Report name (In Japanese)低用量ダイオキシン類による内分泌かく乱作用
Technology summary (In Japanese)感受性が極めて高い妊娠から出生までの時期に,比較的低濃度のダイオキシン類によって,いかなる影響が生じるかを,生殖発生,神経内分泌,行動,免疫機能に対する内分泌かく乱作用の観点から,ラットとマウスを用いて調べた。最も感受性が高い妊娠15日日を中心に,ダイオキシンを単回経口投与し,出生後の発育に伴って観察される影響を検討した。これまでに得られた主な研究結果を,ダイオキシンの体内負荷量との観点から整理した(図1)。極めて低い体内負荷量でステロイドホルモン産生系における変化が観察された。この中には,胎仔や新生仔の脳におけるテストステロン濃度の上昇,アロマターゼ発現量の低下,NMDA受容体発現レベルの変化,あるいは,思春期雄ラットの前立腺腹葉におけるアンドロゲン受容体の発現レベルの減少と5-α還元酵素レベルの上昇など,遺伝子やタンパク質レベルの変化が挙げられる。臓器レベルの変化として外部生殖器重量の減少,肛門生殖突起間距離の短縮,さらに個体レベルの変化として性成熟促進や性行動の変化が観察された。

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Research field
  • Physiology and anatomy of endocrine system
  • Reproductive physiology in general
  • Reproductive (=genital) organs
  • Pollutants
Published papers related (In Japanese)(1)Ikeda M., Inukai N., Mitsui T., Sone H., Yonemoto J., Tohyama C. and Tomita, T. Changes in fetal brain aromatase activity following in utero 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure in rats. Environmental Pharmacology and Toxicology,11:1-7, 2002.
(2)Ishimura R., Ohsako S., Miyabara Y., Sakaue M., Kawakami T., Aoki Y., Yonemoto J. and Tohyama C. Increased glycogen content and glucose transporter 3 mRNA level in placneta of Holtzman rats after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Appl. Pharmacol, 178:161-171, 2002
(3)Jana N.R., Sarkar S., Ishizuka M., Yonemoto J., Tohyama C. and Sone H. Role of Estradiol Receptor-a in differential expression of 2,3,7,8-tetrachlorodibenzo-p-dioxin-inducible genes in the RL95-2 and KLE human endometrial cancer cell lines. Arch. Biochem. Biophys., 368:31-39, 1999.
(4)Jana N.R., Sarkar S., Ishizuka M., Yonemoto J., Tohyama C. and Sone H. Cross-talk between 2,3,7,8-tetrachlorodibenzo-p-dioxin and Testosterone signal transduction pathways in LNCaP prostate cancer cells. Biochem. Biophy. Res. Commun., 256: 462-468, 1999.
(5)Jana N.R., Sarkar, S., Yonemoto, J., Tohyama, C. and Sone, H. Strain Differences in cytochrome P4501A1 gene expression caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat liver: Role of the aryl hydrocarbon receptor and its nuclear translaocator. Biochem. Biophys. Res. Commun, 248:554-558, 1998.
(6)Nohara K., Fujimaki H., Tsukumo S., Ushio H., Miyabara Y., Kijima M., Tohyama C. and Yonemoto J. The effects of perinatal exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin on modifier. J. Risk, Res., 2(2): 151-166, 1999.
(7)Nohara K., Ushio H., Tsukumo S., Kobayashi T., Kijima M., Tohyama C. and Fujimaki H. Alterations of thymocyte development, thymic emigrants and peripheral T cell population in rats exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicology, 145:227-235, 2000.
(8)Ohsako S., Miyabara Y., Nishimura N., Kurosawa S., Sakaue M., Ishimura R., Sato M., Aoki Y., Sone H., Tohyama C., and Yonemoto J. Maternal exposure to a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppressed the development of reproductive organs of male rats: dose-dependent increase of mRNA levels of 5α-reductase type 2 in contrast to decrease of androgen receptor in the pubertal ventral prostate. Toxicol. Sci., 60: 132-143, 2001.
(9)Sarkar S., Jana N.R., Yonemoto J., Tohyama C. and Sone H. Estrogen enhances induction of cytochrome P-4501A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin in liver of female Long-Evans rats. Int. J. Oncol., 16: 141-147, 2000.
(10)Sone H, Tohyama C, Aoki Y and Yonemoto J. Risk assessment of the flavonoids, quercetin as an endocrine
(11)Takanaga H., Kunimoto M., Adachi T., Tohyama C. and Aoki Y. Inhibitory Effect of 2,3,7,8-Tetrachlorodibenzo-p-dioxin on camp-induced Differentiation of Rat C6 Glial Cell Line. J. Neurosci. Res., 64(4):402-409, 2001.
(12)Tsutsumi O., Uechi H., Sone H., Yonemoto J., Takai Y., Momoeda M., Tohyama C., Hashimoto S., Morita M. and Taketani Y. Presence of dioxins in human follicular fluid: Their possible stage-specific action on the development of preimplantation mouse embryos. Biophys. Res. Commun., 250: 498-501, 1998.
Research project
  • Core Research for Evolutional Science and Technology;Endocrine Disrupters
Information research report
  • (In Japanese)遠山 千春. 低用量ダイオキシン類による内分泌かく乱作用と健康リスク. 戦略的基礎研究推進事業 内分泌かく乱物質 第1回領域シンポジウム 講演要旨集 ,2001. p.37 - 51.