Dysregulation of estrogen receptor beta (ERβ), aromatase (CYP19A1), and ER co-activators in the middle frontal gyrus of autism spectrum disorder subjects.
Dysregulation of estrogen receptor beta (ERβ), aromatase (CYP19A1), and ER co-activators in the middle frontal gyrus of autism spectrum disorder subjects.
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自闭症谱系障碍受试者中部回旋中雌激素受体β（ERβ），芳香酶（CYP19A1）和ER共激活剂的失调。
DOI：
10.1186/2040-2392-5-46
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发表时间：
2014
期刊：
影响因子：
6.2
通讯作者：
Pillai A
中科院分区：
文献类型：
--
作者：
Crider A;Thakkar R;Ahmed AO;Pillai A
自闭症谱系障碍（ASD）在男性中比女性更常见。雌激素受体（ER）信号通路中的分子改变可能导致ASD的性别差异，但这种异常在大脑中的程度尚不清楚。使用死后额中回组织（13例ASD和13例对照受试者）。Western blotting检测蛋白质水平。通过qRT-PCR测定基因表达。基因表达分析发现ASD患者额中回ERβ mRNA表达减少35%。此外，在ASD受试者中观察到芳香化酶（CYP 19 A1）mRNA表达降低38%。我们还发现，与对照组相比，ASD受试者的ER共激活因子显著降低，其中SRC-1降低34%，CBP降低77%，P/CAF mRNA水平降低52%。ASD患者额中回TIF-2、AIB-1（ER辅激活因子）、ER辅抑制因子（SMRT和nCoR）和ERα的mRNA水平与对照组相比无差异。我们观察到研究受试者中ERβ、CYP 19 A1和共激活因子之间存在显著相关性。免疫印迹分析进一步证实了对照组和ASD受试者中ERβ和芳香化酶在蛋白水平上的变化。这些结果首次提供了ASD患者脑中ERβ和辅助因子失调的证据。本文的在线版本（doi：10.1186/2040-2392-5-46）包含补充材料，可供授权用户使用。
Autism spectrum disorders (ASD) are much more common in males than in females. Molecular alterations within the estrogen receptor (ER) signaling pathway may contribute to the sex difference in ASD, but the extent of such abnormalities in the brain is not known. Postmortem middle frontal gyrus tissues (13 ASD and 13 control subjects) were used. The protein levels were examined by western blotting. The gene expression was determined by qRT-PCR. Gene expression analysis identified a 35% decrease in ERβ mRNA expression in the middle frontal gyrus of ASD subjects. In addition, a 38% reduction in aromatase (CYP19A1) mRNA expression was observed in ASD subjects. We also found significant decreases in ER co-activators that included a 34% decrease in SRC-1, a 77% decrease in CBP, and a 52% decrease in P/CAF mRNA levels in ASD subjects relative to controls. There were no differences in the mRNA levels of TIF-2, AIB-1 (ER co-activators), ER co-repressors (SMRT and nCoR) and ERα in the middle frontal gyrus of ASD subjects as compared to controls. We observed significant correlations between ERβ, CYP19A1, and co-activators in the study subjects. Immunoblot analysis further confirmed the changes in ERβ and aromatase at the protein level in the control and ASD subjects. These results, for the first time, provide the evidence of the dysregulation of ERβ and co-factors in the brain of subjects with ASD. The online version of this article (doi:10.1186/2040-2392-5-46) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Sarachana T;Xu M;Wu RC;Hu VW
通讯作者：
Hu VW
影响因子：
10.6
作者：
Carper, RA;Courchesne, E
通讯作者：
Courchesne, E
DOI：
10.1073/pnas.94.16.8836
发表时间：
1997-08-05
影响因子：
11.1
作者：
Berman, KF;Schmidt, PJ;Weinberger, DR
通讯作者：
Weinberger, DR
影响因子：
9.8
作者：
Baron-Cohen S;Lombardo MV;Auyeung B;Ashwin E;Chakrabarti B;Knickmeyer R
通讯作者：
Knickmeyer R
影响因子：
3.8
作者：
Auyeung, Bonnie;Knickmeyer, Rebecca;Baron-Cohen, Simon
通讯作者：
Baron-Cohen, Simon