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首页> 外文期刊>Journal of neuroendocrinology >Sex difference in the expression of DNA methyltransferase 3a in the rat amygdala during development.
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Sex difference in the expression of DNA methyltransferase 3a in the rat amygdala during development.

机译：发育过程中大鼠杏仁核中DNA甲基转移酶3a表达的性别差异。

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Sexual differentiation of the neonatal rat brain is regulated by dynamic processes occurring at the level of DNA, resulting in sexually dimorphic gene expression. Steroid hormone receptors act partly in the developing brain by recruiting co-activators, thereby increasing the acetylation of histones and gene expression. Recent data indicate that sexual differentiation of the brain may also result, in part, from differences in promoter methylation patterns of some steroid responsive genes. Methylation of DNA is an epigenetic process that can decrease gene expression without altering the original DNA sequence. DNA cytosine-5-methyltransferases (DNMTs) 1 and 3a are two factors that induce methylation. We investigated whether sex differences in the expression of DNMT1 and DNMT3a were apparent in the amygdala, preoptic area and medial basal hypothalamus at different time points during development. We found that females express significantly more DNMT3a mRNA and protein in the amygdala but not within the preoptic area or the medial basal hypothalamus at postnatal day 1. There were no sex differences in DNMT3a mRNA or protein at postnatal day 10. Furthermore, no sex differences were observed in the expression of DNMT1 at either time point. Because most sex differences in the brain are a result of a higher level of gonadal steroid hormone exposure in males at birth, we examined whether dihydrotestosterone or oestradiol exposure would reduce DNMT3a expression in neonatal female rats. We found that both oestradiol and dihydrotestosterone treatment significantly reduced DNMT3a, but not DNMT1, mRNA expression within the developing amygdala. Our results indicate that sex differences in DNMT3a within the developing amygdala are partly a result of steroid exposure. This suggests that steroid hormone exposures may programme lasting differences in amygdala function by altering the expression of the epigenetic factor, DNMT3a.
机译：新生大鼠大脑的性别分化受DNA水平上发生的动态过程调节，从而导致性二态性基因表达。类固醇激素受体通过募集共激活剂在发育中的大脑中发挥部分作用，从而增加组蛋白的乙酰化和基因表达。最近的数据表明，大脑的性别分化也可能部分是由于某些类固醇反应基因的启动子甲基化模式的差异所致。 DNA的甲基化是一种表观遗传过程，可以在不改变原始DNA序列的情况下降低基因表达。 DNA胞嘧啶5-甲基转移酶（DNMT）1和3a是诱导甲基化的两个因素。我们调查了在发育过程中不同时间的杏仁核，视前区和内侧基底下丘脑中DNMT1和DNMT3a表达的性别差异是否明显。我们发现雌性在出生后第1天在杏仁核中表达明显更多的DNMT3a mRNA和蛋白，但在视前区或内侧下丘脑内侧表达不明显。在出生后第10天，DNMT3a mRNA或蛋白没有性别差异。在任一时间点，在DNMT1的表达中观察到了N-末端。由于大脑中的大多数性别差异是雄性出生时性激素水平升高的结果，因此我们检查了二氢睾丸激素或雌二醇暴露是否会降低新生雌性大鼠中DNMT3a的表达。我们发现，雌二醇和二氢睾丸激素治疗均能显着降低发育中的杏仁核内的DNMT3a，但不降低DNMT1，mRNA表达。我们的结果表明，发育中的杏仁核中DNMT3a的性别差异部分是类固醇暴露的结果。这表明类固醇激素暴露可能会通过改变表观遗传因子DNMT3a的表达而在杏仁核功能中造成持久差异。

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