Evidence that GABAergic neurons in the preoptic area of the rat brain are targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin during development.
Evidence that GABAergic neurons in the preoptic area of the rat brain are targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin during development.
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DOI：
10.1289/ehp.02110s3369
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发表时间：
2002-06
影响因子：
10.4
通讯作者：
Petersen SL
中科院分区：
文献类型：
--
作者：
Hays LE;Carpenter CD;Petersen SL
发育过程中暴露于2，3，7，8-四氯二苯并-对二恶英(TCDD)会干扰男性性行为的男性化和去女性化以及促性腺激素的释放模式。我们以前证明了编码芳烃受体(AhR)的mRNA，一种介导TCDD效应的蛋白质，在控制生殖功能的大脑区域被发现，最明显的是在视前区(POA)。AhR基因的分布模式与合成γ-氨基丁酸(GABA)所必需的谷氨酸脱羧酶(GAD)67紧密重叠。为了验证POA中的GABA能神经元是TCDD发育过程中的靶点的假设，我们使用双标记原位杂交组织化学(ISHH)对GAD和AhR mRNAs在该地区进行了共定位。此外，我们还用ISHH法检测了TCDD(1微克/千克体重，妊娠第15天)对出生后第3天检查的幼鼠POA区GAD-67基因表达的影响。我们发现，几乎所有的POA内的GABA能神经元都表达AhR基因。此外，在POA/前腹侧脑室周围核(rPOA/AVPV)和视前内侧核(MPN)的吻侧部分，女性GAD-67mRNA的表达水平高于男性。TCDD消除了rPOA/AVPV的性别差异，但对嘴端MPN无影响。在尾侧MPN，GAD-67基因的表达没有性别差异，但TCDD抑制了男性的表达。我们的发现表明，大脑中的GABA能神经元是TCDD的靶标，并可能介导这种污染物对生殖功能的发育影响。
Developmental exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) interferes with masculinization and defeminization of male sexual behaviors and gonadotropin release patterns. We previously demonstrated that the mRNA encoding the arylhydrocarbon receptor (AhR), a protein that mediates TCDD effects, is found in brain regions that control reproductive functions, most notably in the preoptic area (POA). The pattern of distribution of the AhR gene closely overlaps that of an enzyme necessary for Gamma-aminobutyric acid (GABA) synthesis, glutamic acid decarboxylase (GAD) 67. To test the hypothesis that GABAergic neurons in the POA are targets of TCDD during development, we used dual-label in situ hybridization histochemistry (ISHH) to co-localize GAD and AhR mRNAs in the region. In addition, we used ISHH to determine the effects of TCDD (1 microg/kg body weight, gestational day 15) on GAD 67 gene expression in POA regions in pups examined on postnatal day 3. We found that virtually all GABAergic neurons in the POA expressed the AhR gene. Furthermore, GAD 67 mRNA levels were higher in females than in males in the rostral POA/anteroventral periventricular nucleus (rPOA/AVPV) and in the rostral portion of the medial preoptic nucleus (MPN). TCDD abolished sex differences in the rPOA/AVPV but had no effect in the rostral MPN. In the caudal MPN, there were no sex differences in GAD 67 gene expression, but TCDD depressed expression specifically in males. Our findings demonstrate that GABAergic neurons in the brain are targets of TCDD and may mediate developmental effects of this contaminant on reproductive function.
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二恶英毒性的机制：与风险评估的关系。
影响因子：
10.4
作者：
Birnbaum, L S
通讯作者：
Birnbaum, L S
影响因子：
2.9
作者：
Gao, B;Moore, RY
通讯作者：
Moore, RY
影响因子：
16.2
作者：
ERLANDER, MG;TILLAKARATNE, NJK;TOBIN, AJ
通讯作者：
TOBIN, AJ
DOI：
10.1073/pnas.89.17.8185
发表时间：
1992-09-01
影响因子：
11.1
作者：
BURBACH, KM;POLAND, A;BRADFIELD, CA
通讯作者：
BRADFIELD, CA
影响因子：
1.9
作者：
GRAY, P;BROOKS, PJ
通讯作者：
BROOKS, PJ