PMID- 22493514
OWN - NLM
STAT- MEDLINE
DCOM- 20120815
LR  - 20211021
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 287
IP  - 22
DP  - 2012 May 25
TI  - Dioxin silences gonadotropin expression in perinatal pups by inducing histone 
      deacetylases: a new insight into the mechanism for the imprinting of sexual 
      immaturity by dioxin.
PG  - 18440-50
LID - 10.1074/jbc.M111.335158 [doi]
AB  - Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) causes the 
      impairment of reproduction and development in the pups. Our previous studies have 
      revealed that maternal treatment with TCDD attenuates the fetal production of 
      pituitary gonadotropins (luteinizing hormone (LH) and follicle-stimulating 
      hormone) at gestational day (GD) 20, leading to the impairment of sexual behavior 
      in adulthood. However, the mechanism underlying such a reduction has remained 
      unknown until now. When pregnant rats at GD15 were given an oral dose of TCDD (1 
      mug/kg), the testicular expression of steroidogenic proteins was reduced between 
      GD20 and postnatal days (PND) 2. In accordance with this, the pituitary 
      expression of gonadotropin beta-subunit and serum gonadotropin were also attenuated 
      from GD20 to PND0 in a pup-specific fashion. To identify the target genes linked 
      to a fetal reduction in gonadotropin beta-subunit, we performed a DNA microarray 
      analysis using the fetal pituitary and its regulatory organ, the hypothalamus. 
      The results obtained showed that TCDD induced histone deacetylases (HDACs) in the 
      fetal pituitary. In support with this, TCDD markedly deacetylated histones H3 and 
      H4 twined around the promoter of the fetal LHbeta gene. This effect was fetus- and 
      LHbeta-specific, and this was not observed in the maternal pituitary or for other 
      pituitary hormone genes. Finally, an LHbeta reduction caused by TCDD was completely 
      restored by maternal co-treatment with valproic acid, an HDAC inhibitor. These 
      results strongly suggest that the increased deacetylation of histone owing to 
      HDAC induction plays a critical role in the TCDD-induced reduction in LHbeta in the 
      fetal pituitary.
FAU - Takeda, Tomoki
AU  - Takeda T
AD  - Graduate School of Pharmaceutical Sciences, Kyushu University, Higashi-ku, 
      Fukuoka, Japan.
FAU - Fujii, Misaki
AU  - Fujii M
FAU - Taura, Junki
AU  - Taura J
FAU - Ishii, Yuji
AU  - Ishii Y
FAU - Yamada, Hideyuki
AU  - Yamada H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120409
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Gonadotropins)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Steroids)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Chromatin Immunoprecipitation
MH  - DNA Methylation
MH  - Enzyme Induction
MH  - Epigenesis, Genetic
MH  - Female
MH  - Gonadotropins/*metabolism
MH  - Histone Deacetylases/*biosynthesis
MH  - Male
MH  - Molecular Sequence Data
MH  - Oligonucleotide Array Sequence Analysis
MH  - Pituitary Gland/drug effects/embryology
MH  - Polychlorinated Dibenzodioxins/*pharmacology
MH  - Pregnancy
MH  - Rats
MH  - Rats, Wistar
MH  - *Sexual Maturation
MH  - *Steroids/biosynthesis
PMC - PMC3365744
EDAT- 2012/04/12 06:00
MHDA- 2012/08/16 06:00
PMCR- 2013/05/25
CRDT- 2012/04/12 06:00
PHST- 2012/04/12 06:00 [entrez]
PHST- 2012/04/12 06:00 [pubmed]
PHST- 2012/08/16 06:00 [medline]
PHST- 2013/05/25 00:00 [pmc-release]
AID - S0021-9258(20)50086-0 [pii]
AID - M111.335158 [pii]
AID - 10.1074/jbc.M111.335158 [doi]
PST - ppublish
SO  - J Biol Chem. 2012 May 25;287(22):18440-50. doi: 10.1074/jbc.M111.335158. Epub 
      2012 Apr 9.