著者

山田 英之 武田 知起 古賀 貴之 石井 祐次

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.134, no.4, pp.529-535, 2014 (Released:2014-04-01)

参考文献数

28

被引用文献数

3

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The sexual differentiation of animal fetuses and infants needs stimuli by sex steroids, which are produced in their own gonads, during a short window (‘critical period’) of pre- and post-natal periods. Our laboratory has conducted a series of studies focusing on the damage to next generations by dioxins. When pregnant rats are exposed to a prototype of dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 1 μg/kg), sexual immaturity such as defects in copulation behavior as well as growth retardation emerges in their pups. We have provided evidence that such disorders are evoked, if not all, from a transient reduction in the gonadal synthesis of sex steroids in fetuses/infants during the critical period. Our studies also revealed that TCDD initially reduces the pituitary expression of luteinizing hormone (LH) to exert the effect on steroidogenesis. Several mechanisms seem to be involved in a TCDD-induced reduction in LH expression. For example, a change in epigenetic regulation in the pituitary and impaired energy production in the hypothalamus are suggested to contribute to the above reduction. Current our study has demonstrated that a transient reduction in the pituitary-gonad axis fixes the lowered expression of hypothalamic gonadotropin-releasing hormone, resulting in defects in sexual behavior. Through these topics, we discuss the role of the critical period in differentiation and development.

著者

山田 英之 小栗 一太

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.34, no.9, pp.895-899, 1998-09-01 (Released:2018-08-26)

参考文献数

24

著者

山田 健一 石井 祐次 武田 知起 黒木 廣明 三苫 千景 内 博史 古江 増隆 山田 英之

出版者

福岡医学会

雑誌

福岡医学雑誌 = Fukuoka acta medica (ISSN:0016254X)

巻号頁・発行日

vol.106, no.5, pp.169-175, 2015-05-25

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The effect of cynaropicrin that is the major component of an edible plant, artichoke (Cynarascolymus) on 2,3,4,7,8-pentachlorodibenzofuran (PenCDF)-induced toxicity in mice was studied. We evaluated the effect of cynaropicrin on the wasting syndrome and oxidative stress elicited by PenCDF. However, the PenCDF dose-response relationship on the wasting syndrome has been superficial. Therefore, we determined the dose which causes wasting syndrome in C57BL/6J m ice, a responsive strain to dioxins. Since 2,3,7,8-tetrachlorodibenzo-p-dioxin (0.1 mg/kg, p.o.) induces hepatic ethoxyresorfin O-deethylase (EROD) activity in mice, we set the doses of PenCDF at 0.3, 1.0, 3.0, 5.0 and 10 mg/kg (once, p.o.) on the basis of its toxic-eqivalency factor (0.3). The wasting syndrome was evaluated by measuring the daily changes of body weight. Thiobarbituric acid-reactive substances were used as an index of oxidative stress. Of PenCDF doses examined, wasting syndrome and oxidative stress took place most markedly in 5 mg/kg. In disagreement with this, EROD activity which is the marker of the aryl hydrocarbon receptor-dependent induction of cytochrome P450 1a1 was elevated most abundantly at 0.3 mg/kg. Then, we examined the effect of cynaropicrin on the wasting syndrome and oxidative stress provoked by PenCDF at 5 mg/kg. However, this compound up to 20 mg/kg (p.o.) did not attenuate PenCDF-induced wasting syndrome. On the contray, PenCDF-induced oxidateive stress was suppressed by cynaropicrin at the highest dose (20 mg/kg), although EROD activity was increased rather than reduced by cynaropicrin at lower doses. Thus, it is suggested that cynaropicrin has an ability to reduce oxidative stress caused by PenCDF.

著者

山田 英之 福島 直 小栗 一太

出版者

日本毒性学会

雑誌

Journal of toxicological sciences (ISSN:03881350)

巻号頁・発行日

vol.23, pp.App.161-App.170, 1998-11-26

参考文献数

39