Journal
JOURNAL OF TOXICOLOGICAL SCIENCES
Volume 36, Issue 2, Pages 221-229Publisher
JAPANESE SOC TOXICOLOGICAL SCIENCES
DOI: 10.2131/jts.36.221
Keywords
Tetrachlorodibenzo-p-dioxin (TCDD); Pituitary; Fetus; Gonadotropin-releasing hormone; Protein kinase; Gonadotropin beta-subunit
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Funding
- Ministry of Health, Labour and Welfare, Japan [H21-Kagaku-Ippan-005]
- Japan Society for the Promotion of Science [19390034]
- Grants-in-Aid for Scientific Research [19390034] Funding Source: KAKEN
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Our previous studies have demonstrated that maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes a reduction in gonadotropin biosynthesis in the fetal pituitary, resulting in the attenuated expression of steroidogenic proteins in the fetal gonads and the impairment of sexual behaviors in adulthood. However, the mechanism of the attenuation remains unknown. To address this issue, we investigated whether TCDD affects the pituitary production of gonadotropins, using cultured pituitary. In the absence of gonadotropin-releasing hormone (GnRH), a regulator of gonadotropin biosynthesis, TCDD did not affect the expression of gonadotropin mRNAs both in fetal and postnatal pituitaries. On the other hand, in the presence of GnRH, TCDD interfered with the synthesis of gonadotropin beta-subunit mRNAs only in the fetal pituitary. A protein kinase C (PKC) activator (phorbol 12-myristate 13-acetate) and a PKA activator (8-bromoadenosine-3' 5'-cyclic monophosphate) induced the expression of gonadotropin mRNAs in the fetal pituitary. Among the subunits, only the induction of beta-subunit was reduced by TCDD treatment. These results suggest that TCDD reduces gonadotropin biosynthesis via damage to GnRH-stimulated PKC and PKA signaling in a beta-subunit- and fetal age-specific manner.
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