Sex Differences in Epigenetic Regulation of the Estrogen Receptor-α Promoter within the Developing Preoptic Area
Sex Differences in Epigenetic Regulation of the Estrogen Receptor-α Promoter within the Developing Preoptic Area
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DOI：
10.1210/en.2009-0649
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发表时间：
2010-05-01
期刊：
影响因子：
4.8
通讯作者：
Auger, Anthony P.
中科院分区：
文献类型：
--
作者：
Kurian, Joseph R.;Olesen, Kristin M.;Auger, Anthony P.
大脑中的性别差异在很大程度上是由男性出生后不久睾丸激素激增造成的。虽然这种激素激增是短暂的，但大脑和行为的性别差异是持久的。在这里，我们描述了发育中的大鼠视前区内雌激素受体α（ER α）启动子区域DNA甲基化的性别差异，雄性比雌性在ER α启动子内表现出更多的DNA甲基化。更重要的是，我们报告说，模拟母亲梳理，一种形式的母亲的互动，是性二态性与男性经历比女性在新生儿时期，有效地男性化女性ER α启动子甲基化和基因表达。这表明，针对男性与女性的孕产妇护理的自然变化可以通过创建性二态DNA甲基化模式来影响大脑中的性别差异。我们还发现，早期雌二醇暴露可能有助于DNA甲基化模式的性别差异。这表明，早期的社会互动和雌二醇暴露可能会在基因组中聚集，通过表观遗传分化来组织大脑中持久的性别差异。（内分泌学151：2297-2305，2010）
Sex differences in the brain are largely organized by a testicular hormone surge that occurs in males shortly after birth. Although this hormone surge is transient, sex differences in brain and behavior are lasting. Here we describe a sex difference in DNA methylation of the estrogen receptor-alpha (ER alpha) promoter region within the developing rat preoptic area, with males exhibiting more DNA methylation within the ER alpha promoter than females. More importantly, we report that simulating maternal grooming, a form of maternal interaction that is sexually dimorphic with males experiencing more than females during the neonatal period, effectively masculinizes female ER alpha promoter methylation and gene expression. This suggests natural variations in maternal care that are directed differentially at males vs. females can influence sex differences in the brain by creating sexually dimorphic DNA methylation patterns. We also find that the early estradiol exposure may contribute to sex differences in DNA methylation patterns. This suggests that early social interaction and estradiol exposure may converge at the genome to organize lasting sex differences in the brain via epigenetic differentiation. (Endocrinology 151: 2297-2305, 2010)