PMID- 19276399
OWN - NLM
STAT- MEDLINE
DCOM- 20090623
LR  - 20161125
IS  - 1521-0103 (Electronic)
IS  - 0022-3565 (Linking)
VI  - 329
IP  - 3
DP  - 2009 Jun
TI  - Maternal exposure to dioxin disrupts gonadotropin production in fetal rats and 
      imprints defects in sexual behavior.
PG  - 1091-9
LID - 10.1124/jpet.109.151282 [doi]
AB  - 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 microg/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.
FAU - Takeda, Tomoki
AU  - Takeda T
AD  - Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, 
      Higashi-ku, Fukuoka 812-8582, Japan.
FAU - Matsumoto, Yuki
AU  - Matsumoto Y
FAU - Koga, Takayuki
AU  - Koga T
FAU - Mutoh, Junpei
AU  - Mutoh J
FAU - Nishimura, Yoshio
AU  - Nishimura Y
FAU - Shimazoe, Takao
AU  - Shimazoe T
FAU - Ishii, Yuji
AU  - Ishii Y
FAU - Ishida, Takumi
AU  - Ishida T
FAU - Yamada, Hideyuki
AU  - Yamada H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090310
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Chorionic Gonadotropin)
RN  - 0 (Gonadotropins, Pituitary)
RN  - 0 (Phosphoproteins)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (steroidogenic acute regulatory protein)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - EC 1.14.14.19 (Steroid 17-alpha-Hydroxylase)
SB  - IM
MH  - Animals
MH  - Body Weight/drug effects
MH  - Chorionic Gonadotropin/pharmacology/therapeutic use
MH  - Disorders of Sex Development/etiology/prevention & control
MH  - Female
MH  - Fetus/*drug effects/metabolism
MH  - Follicle Stimulating Hormone/blood/genetics
MH  - Gene Expression/drug effects
MH  - Gonadotropins, Pituitary/blood/genetics/*metabolism
MH  - Luteinizing Hormone/blood/genetics
MH  - Male
MH  - Maternal Exposure/*adverse effects
MH  - Ovary/drug effects/growth & development/metabolism
MH  - Phosphoproteins/genetics/metabolism
MH  - Pituitary Gland/drug effects/metabolism
MH  - Polychlorinated Dibenzodioxins/*pharmacology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*etiology/prevention & control
MH  - Prostate/drug effects/growth & development
MH  - Rats
MH  - Rats, Wistar
MH  - Sexual Behavior, Animal/*drug effects
MH  - Steroid 17-alpha-Hydroxylase/genetics/metabolism
MH  - Testis/drug effects/metabolism
EDAT- 2009/03/12 09:00
MHDA- 2009/06/24 09:00
CRDT- 2009/03/12 09:00
PHST- 2009/03/12 09:00 [entrez]
PHST- 2009/03/12 09:00 [pubmed]
PHST- 2009/06/24 09:00 [medline]
AID - jpet.109.151282 [pii]
AID - 10.1124/jpet.109.151282 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2009 Jun;329(3):1091-9. doi: 10.1124/jpet.109.151282. Epub 
      2009 Mar 10.