PMID- 24132183
OWN - NLM
STAT- MEDLINE
DCOM- 20140303
LR  - 20161125
IS  - 1521-0111 (Electronic)
IS  - 0026-895X (Linking)
VI  - 85
IP  - 1
DP  - 2014 Jan
TI  - Maternal exposure to dioxin imprints sexual immaturity of the pups through fixing 
      the status of the reduced expression of hypothalamic gonadotropin-releasing 
      hormone.
PG  - 74-82
LID - 10.1124/mol.113.088575 [doi]
AB  - Our previous studies have shown that treatment of pregnant rats with 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; 1 mug/kg) at gestational day (GD) 15 
      reduces the pituitary synthesis of luteinizing hormone (LH) during the late fetal 
      and early postnatal period, leading to the imprinting of defects in sexual 
      behaviors at adulthood. However, it remains unclear how the attenuation of 
      pituitary LH is linked to sexual immaturity. To address this issue, we performed 
      a DNA microarray analysis to identify the gene(s) responsible for dioxin-induced 
      sexual immaturity on the pituitary and hypothalamus of male pups, born of 
      TCDD-treated dams, at the age of postnatal day (PND) 70. Among the reduced genes, 
      we focused on gonadotropin-releasing hormone (GnRH) in the hypothalamus because 
      of published evidence that it has a role in sexual behaviors. An attenuation by 
      TCDD of GnRH expression emerged at PND4, and no subsequent return to the control 
      level was seen. A change in neither DNA methylation nor histone acetylation 
      accounted for the reduced expression of GnRH. Intracerebroventricular infusion of 
      GnRH to the TCDD-exposed pups after reaching maturity restored the impairment of 
      sexual behaviors. Supplying equine chorionic gonadotropin, an LH-mimicking 
      hormone, to the TCDD-exposed fetuses at GD15 resulted in a recovery from the 
      reduced expression of GnRH, as well as from the defects in sexual behavior. These 
      results strongly suggest that maternal exposure to TCDD fixes the status of the 
      lowered expression of GnRH in the offspring by reducing the LH-assisted 
      steroidogenesis at the perinatal stage, and this mechanism imprints defects in 
      sexual behaviors at adulthood.
FAU - Takeda, Tomoki
AU  - Takeda T
AD  - Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan 
      (T.T., M.F., Y.H., T.S., Y.I., H.Y.); and Faculty of Pharmaceutical Sciences, 
      Nagasaki International University, Sasebo, Japan (M.Y., M.H.).
FAU - Fujii, Misaki
AU  - Fujii M
FAU - Hattori, Yukiko
AU  - Hattori Y
FAU - Yamamoto, Midori
AU  - Yamamoto M
FAU - Shimazoe, Takao
AU  - Shimazoe T
FAU - Ishii, Yuji
AU  - Ishii Y
FAU - Himeno, Masaru
AU  - Himeno M
FAU - Yamada, Hideyuki
AU  - Yamada H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131016
PL  - United States
TA  - Mol Pharmacol
JT  - Molecular pharmacology
JID - 0035623
RN  - 0 (Chorionic Gonadotropin)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 33515-09-2 (Gonadotropin-Releasing Hormone)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Chorionic Gonadotropin/therapeutic use
MH  - DNA Methylation
MH  - Embryo, Mammalian
MH  - Environmental Pollutants/*toxicity
MH  - Female
MH  - Genomic Imprinting
MH  - Gonadotropin-Releasing Hormone/genetics/*metabolism/therapeutic use
MH  - Horses
MH  - Hypothalamus/*metabolism
MH  - Male
MH  - Maternal Exposure/*adverse effects
MH  - Maternal-Fetal Exchange
MH  - Pituitary Gland/metabolism
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/drug therapy/etiology/*psychology
MH  - Rats
MH  - Rats, Wistar
MH  - *Sexual Behavior, Animal/drug effects
MH  - Testis/metabolism
MH  - Time Factors
EDAT- 2013/10/18 06:00
MHDA- 2014/03/04 06:00
CRDT- 2013/10/18 06:00
PHST- 2013/10/18 06:00 [entrez]
PHST- 2013/10/18 06:00 [pubmed]
PHST- 2014/03/04 06:00 [medline]
AID - mol.113.088575 [pii]
AID - 10.1124/mol.113.088575 [doi]
PST - ppublish
SO  - Mol Pharmacol. 2014 Jan;85(1):74-82. doi: 10.1124/mol.113.088575. Epub 2013 Oct 
      16.