title: 2,3,4,7,8-Pentachlorodibenzofuran is far less potent than 2,3,7,8-tetrachlorodibenzo-p-dioxin in disrupting the pituitary-gonad axis of the rat fetus.
abstract: The effect of 2,3,4,7,8-pentachlorodibenzofuran (PnCDF) on the fetal pituitary-gonad axis was compared with that produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Wistar rats. Maternal treatment at gestational day (GD) 15 with PnCDF and TCDD reduced the fetal expression at GD20 of pituitary luteinizing hormone (LH) and the testicular proteins necessary for steroidogenesis. The relative potencies of PnCDF ranged from 1/42nd to 1/63rd of the TCDD effect. While PnCDF, at a dose sufficient to cause a reduction in fetal LH, provoked defects in sexual behavior at adulthood, a dose less than the ED50 failed to produce any abnormality. There was a loss of fetal body weight following in utero exposure to PnCDF, and the effect of PnCDF was also much less than that of TCDD. The disturbance in fetal growth was suggested to be due to a reduction in the level of fetal growth hormone (GH) by dioxins. The disorder caused by PnCDF/TCDD in the fetal pituitary-gonad axis occurred at doses less than those needed to cause wasting syndrome in pubertal rats. The harmful effect of PnCDF relative to TCDD was more pronounced in fetal rats than in pubertal rats. These lines of evidence suggest that: 1) PnCDF as well as TCDD imprints defects in sexual behavior by disrupting the fetal pituitary-gonad axis; 2) these dioxins hinder fetal growth by reducing the expression of fetal GH; and 3) the fetal effects of PnCDF/TCDD are more sensitive than sub-acute toxicity during puberty, and the relative effect of PnCDF varies markedly depending on the indices used.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Junki
authors.initials: J
authors.lastname: Taura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Fujii
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Daiichi University of Pharmacy, Fukuoka, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kuroki
authors.affiliation: Department of Obstetrics, Fukuoka Children's Hospital, Fukuoka, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Tsukimori
authors.affiliation: Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchi
authors.affiliation: Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, Fukuoka, Japan; Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Masutaka
authors.initials: M
authors.lastname: Furue
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. Electronic address: hyamada@phar.kyushu-u.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamada
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity; D005260:Female; D047109:Fetal Development / Q000187:drug effects / Q000502:physiology; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D018811:Maternal Exposure; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012726:Sexual Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D013737:Testis / Q000187:drug effects* / Q000502:physiology
chemical_list: D001572:Benzofurans; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D007986:Luteinizing Hormone; C038890:2,3,4,7,8-pentachlorodibenzofuran
keywords: 2,3,4,7,8-Pentachlorodibenzofuran (PnCDF); 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD); Fetus; Gonadotropin; Steroidogenesis; Toxic equivalency factor (TEF)