Department of Psychology, University of Wisconsin-Madison, 1202 West Johnson Street, Madison, Wisconsin 53706, USA.
Endocrinology. 2010 Mar;151(3):1212-20. doi: 10.1210/en.2009-0594. Epub 2010 Jan 5.
Nuclear receptor function on DNA is regulated by the balanced recruitment of coregulatory complexes. Recruited proteins that increase gene expression are called coactivators, and those that decrease gene expression are called corepressors. Little is known about the role of corepressors, such as nuclear receptor corepressor (NCoR), on the organization of behavior. We used real-time PCR to show that NCoR mRNA levels are sexually dimorphic, that females express higher levels of NCoR mRNA within the developing amygdala and hypothalamus, and that NCoR mRNA levels are reduced by estradiol treatment. To investigate the functional role of NCoR on juvenile social behavior, we infused small interfering RNA targeted against NCoR within the developing rat amygdala and assessed the enduring impact on juvenile social play behavior, sociability, and anxiety-like behavior. As expected, control males exhibited higher levels of juvenile social play than control females. Reducing NCoR expression during development further increased juvenile play in males only. Interestingly, decreased NCoR expression within the developing amygdala had lasting effects on increasing juvenile anxiety-like behavior in males and females. These data suggest that the corepressor NCoR functions to blunt sex differences in juvenile play behavior, a sexually dimorphic and hormone-dependent behavior, and appears critical for appropriate anxiety-like behavior in juvenile males and females.
核受体在 DNA 上的功能受共调节复合物的平衡募集调节。增加基因表达的募集蛋白称为共激活剂,而降低基因表达的募集蛋白称为共抑制剂。关于共抑制剂(如核受体共抑制剂(NCoR))对行为组织的作用知之甚少。我们使用实时 PCR 显示 NCoR mRNA 水平存在性别二态性,雌性在发育中的杏仁核和下丘脑内表达更高水平的 NCoR mRNA,并且 NCoR mRNA 水平受雌二醇处理的降低。为了研究 NCoR 在青少年社交行为中的功能作用,我们在发育中的大鼠杏仁核内注入针对 NCoR 的小干扰 RNA,并评估其对青少年社交玩耍行为、社交性和焦虑样行为的持久影响。正如预期的那样,对照雄性比对照雌性表现出更高水平的青少年社交玩耍。在发育过程中减少 NCoR 表达只会进一步增加雄性的青少年玩耍。有趣的是,在发育中的杏仁核内降低 NCoR 表达对雄性和雌性的青少年焦虑样行为的增加具有持久影响。这些数据表明,共抑制剂 NCoR 可减弱青少年玩耍行为的性别差异,这种行为具有性别二态性和激素依赖性,并且对青少年雄性和雌性的适当焦虑样行为至关重要。