期刊
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
卷 329, 期 3, 页码 1091-1099出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.109.151282
关键词
-
资金
- Ministry of Health, Labour and Welfare, Japan [Research on Food Safety] [H18-012]
- Japan Society for the Promotion of Science [19390034]
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and related substances are a class of environmental pollutants with suspected toxic effects on reproductive and developmental processes. This study investigated a hypothesis that maternal exposure to TCDD damages gonadotropin-regulated steroidogenesis in fetal gonads to imprint defects in sexual behavior as well as the maturation of gonadal tissues. Oral administration of 1 mu g/kg TCDD to pregnant Wistar rats at gestational day (GD) 15 attenuated the expression of luteinizing hormone (LH), a regulator of gonadal steroidogenesis, in the pituitaries of male and female fetuses at GD20. TCDD treatment also reduced the fetal expression of testicular and ovarian steroidogenic proteins, including steroidogenic acute-regulatory protein. These changes in pituitary and gonadal proteins were fetus-specific, and this seems not to be because of the greater delivery of TCDD to the brain of fetuses than adults. This is because a reduction in LH production was not reproduced even although TCDD was administered intraventricularly to adult rats. Direct supplementation of equine chorionic gonadotropin (eCG), an LH-mimicking hormone, to TCDD-exposed fetuses at GD17 restored the reduced expression of gonadal steroidogenic proteins. Maternal exposure to TCDD delayed the development of gonadal tissues in male and female pups and impaired their sexual behavior. However, eCG treatment at the fetal stage again restored not only tissue maturation but also many of the behavioral defects that occurred at adulthood. These results demonstrate that TCDD disrupts steroidogenesis in fetuses by targeting pituitary gonadotropin production and imprints demasculinization in males and defeminization in females in terms of their copulatory behavior.
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