Role of the critical period in sex and brain differentiation: Learning from dioxin-induced disorders in next generations

Hideyuki Yamada, Tomoki Takeda, Takayuki Koga, Yuji Ishii

研究成果: ジャーナルへの寄稿学術誌査読

5 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)529-535
ページ数7
ジャーナルYakugaku Zasshi
134
4
DOI
出版ステータス出版済み - 2014

!!!All Science Journal Classification (ASJC) codes

  • 薬理学
  • 薬科学

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