PMID- 29753751
OWN - NLM
STAT- MEDLINE
DCOM- 20190403
LR  - 20190403
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 154
DP  - 2018 Aug
TI  - The aryl hydrocarbon receptor is indispensable for dioxin-induced defects in 
      sexually-dimorphic behaviors due to the reduction in fetal steroidogenesis of the 
      pituitary-gonadal axis in rats.
PG  - 213-221
LID - S0006-2952(18)30193-X [pii]
LID - 10.1016/j.bcp.2018.05.008 [doi]
AB  - Many forms of the toxic effects produced by dioxins and related chemicals take 
      place following activation of the aryl hydrocarbon receptor (AHR). Our previous 
      studies have demonstrated that treating pregnant rats with 
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a highly toxic dioxin, attenuates the 
      pituitary expression of gonadotropins to reduce testicular steroidogenesis during 
      the fetal stage, resulting in the impairment of sexually-dimorphic behaviors 
      after the offspring reach maturity. To investigate the contribution of AHR to 
      these disorders, we examined the effects of TCDD on AHR-knockout (AHR-KO) Wistar 
      rats. When pregnant AHR-heterozygous rats were given an oral dose of 1 microg/kg TCDD 
      at gestational day (GD) 15, TCDD reduced the expression of pituitary 
      gonadotropins and testicular steroidogenic proteins in male wild-type fetuses at 
      GD20 without affecting body weight, sex ratio and litter size. However, the same 
      defect did not occur in AHR-KO fetuses. Further, fetal exposure to TCDD impaired 
      the activity of masculine sexual behavior after reaching adulthood only in the 
      wild-type offspring. Also, in female offspring, not only the fetal gonadotropins 
      production but also sexual dimorphism, such as saccharin preference, after 
      growing up were suppressed by TCDD only in the wild-type. Interestingly, in the 
      absence of TCDD, deleting AHR reduced masculine sexual behavior, as well as fetal 
      steroidogenesis of the pituitary-gonadal axis. These results provide novel 
      evidence that 1) AHR is required for TCDD-produced defects in sexually-dimorphic 
      behaviors of the offspring, and 2) AHR signaling plays a role in gonadotropin 
      synthesis during the developmental stage to acquire sexual dimorphism after 
      reaching adulthood.
CI  - Copyright (c) 2018 Elsevier Inc. All rights reserved.
FAU - Hattori, Yukiko
AU  - Hattori Y
AD  - Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan; 
      Research Fellow of Japan Society for the Promotion of Science, Tokyo, Japan.
FAU - Takeda, Tomoki
AU  - Takeda T
AD  - Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
FAU - Nakamura, Arisa
AU  - Nakamura A
AD  - Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
FAU - Nishida, Kyoko
AU  - Nishida K
AD  - Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
FAU - Shioji, Yuko
AU  - Shioji Y
AD  - Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
FAU - Fukumitsu, Haruki
AU  - Fukumitsu H
AD  - Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
FAU - Yamada, Hideyuki
AU  - Yamada H
AD  - Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
FAU - Ishii, Yuji
AU  - Ishii Y
AD  - Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan. 
      Electronic address: ishii@phar.kyushu-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180516
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Dioxins)
RN  - 0 (Environmental Pollutants)
RN  - 0 (Gonadotropins, Pituitary)
RN  - 0 (Polychlorinated Dibenzodioxins)
RN  - 0 (Receptors, Aryl Hydrocarbon)
SB  - IM
MH  - Animals
MH  - Dioxins/toxicity
MH  - Environmental Pollutants
MH  - Female
MH  - Gonadotropins, Pituitary/antagonists & inhibitors/metabolism
MH  - Locomotion/drug effects/physiology
MH  - Male
MH  - Pituitary Gland/drug effects/*metabolism
MH  - Polychlorinated Dibenzodioxins/*toxicity
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/chemically induced/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Aryl Hydrocarbon/agonists/*deficiency
MH  - *Sex Characteristics
MH  - Testis/drug effects/*metabolism
OTO - NOTNLM
OT  - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)
OT  - Aryl hydrocarbon receptor knockout (AHR-KO) rat
OT  - Fetus
OT  - Gonadotropin
OT  - Pituitary-gonadal axis
OT  - Sexually-dimorphic behavior
EDAT- 2018/05/14 06:00
MHDA- 2019/04/04 06:00
CRDT- 2018/05/14 06:00
PHST- 2018/03/13 00:00 [received]
PHST- 2018/05/09 00:00 [accepted]
PHST- 2018/05/14 06:00 [pubmed]
PHST- 2019/04/04 06:00 [medline]
PHST- 2018/05/14 06:00 [entrez]
AID - S0006-2952(18)30193-X [pii]
AID - 10.1016/j.bcp.2018.05.008 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2018 Aug;154:213-221. doi: 10.1016/j.bcp.2018.05.008. Epub 
      2018 May 16.