title: Dioxin-induced retardation of development through a reduction in the expression of pituitary hormones and possible involvement of an aryl hydrocarbon receptor in this defect: a comparative study using two strains of mice with different sensitivities to dioxin.
abstract: We have previously revealed that treating pregnant rats with 2,3,7,8-tetracholorodibenzo-p-dioxin (TCDD) reduces the expression of gonadotropins and growth hormone (GH) in the fetal and neonatal pituitary. A change in gonadotropin expression impairs the testicular expression of steroidogenic proteins in perinatal pups, and imprint defects in sexual behavior after reaching maturity. In this study, we examined whether TCDD also affects the expression of gonadotropin and GH in mice using C57BL/6J and DBA/2J strains which express the aryl hydrocarbon receptor (Ahr) exhibiting a different affinity for TCDD. When pregnant C57BL/6J mice at gestational day (GD) 12 were given oral TCDD (0.2-20 μg/kg), all doses significantly attenuated the pituitary expression of gonadotropin mRNAs in fetuses at GD18. On the other hand, in DBA/2J mice, a much higher dose of TCDD (20 μg/kg) was needed to produce a significant attenuation. Such reduction in the C57BL/6J strain continued until at least postnatal day (PND) 4. In agreement with this, TCDD reduced the testicular expression of steroidogenic proteins in C57BL/6J neonates at PND2 and 4, although the same did not occur in the fetal testis and ovary. Furthermore, TCDD reduced the perinatal expression of GH, litter size and the body weight of newborn pups only in the C57BL/6J strain. These results suggest that 1) also in mice, maternal exposure to TCDD attenuates gonadotropin-regulated steroidogenesis and GH expression leading to the impairment of pup development and sexual immaturity; and 2) Ahr activation during the late fetal and early postnatal stages is required for these defects.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Takeda
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Junki
authors.initials: J
authors.lastname: Taura
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Hattori
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Electronic address: hyamada@phar.kyushu-u.ac.jp.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yamada
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000819:agonists* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010902:Pituitary Gland / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D010908:Pituitary Hormones, Anterior / Q000235:genetics / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000378:metabolism; D046468:Sexual Development / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms; D013723:Teratogens / Q000633:toxicity*; D013737:Testis / Q000187:drug effects / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004785:Environmental Pollutants; D010908:Pituitary Hormones, Anterior; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D013723:Teratogens; C484722:Ahr protein, mouse
keywords: 2,3,7.8-Tetrachlorodibenzo-p-dioxin (TCDD); Aryl hydrocarbon receptor; Gonadotropin; Growth hormone; Steroidogenesis