Differential expression and regional distribution of steroid receptor coactivators SRC-1 and SRC-2 in brain and pituitary.

Differential expression and regional distribution of steroid receptor coactivators SRC-1 and SRC-2 in brain and pituitary.
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DOI:
10.1210/endo.141.6.7489
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发表时间:
2000-06
期刊:
影响因子:
4.8
通讯作者:
Onno C. Meijer;P. Steenbergen;E. R. Kloet
Onno C. Meijer;P. Steenbergen;E. R. Kloet
中科院分区:
医学2区
文献类型:
--
作者:
Onno C. Meijer;P. Steenbergen;E. R. Kloet

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类固醇受体共激活蛋白的p160家族成员介导由核受体(包括所有类固醇受体)引起的对基因转录的刺激作用。使用原位杂交,我们研究了类固醇受体辅激活因子1(SRC-1/NCoA-1)和类固醇受体辅激活因子2(SRC-2/NCoA-2/GRIP-1/TIF-2)的两种功能不同的剪接变体的信使RNA(mRNA)的神经解剖分布。这些共激活因子的转录本编码表现出高度差异的表达模式。SRC-2 mRNA在脑中以非常低的水平表达,但在垂体前叶中显示表达。SRC-Ia和Ie mRNA在许多脑区域中表达,包括海马、杏仁核、下丘脑、基底神经节和同皮质。SRC-1a和le表达之间的显著差异在几个脑核团中观察到。SRC-1a mRNA的相对水平在垂体前叶、下丘脑弓状核、室旁核和腹内侧核、蓝斑和三叉神经运动核中高得多,这些都是类固醇激素在大脑中的重要靶点。SRC-le mRNA在尾侧核杏仁核(壳),基底外侧杏仁核和一些丘脑核团中的相对表达适度升高。这些辅激活因子的差异和不均匀的神经解剖学分布可能是脑中类固醇受体介导的信号的多样性和细胞特异性的基础。
Members of the p160 family of steroid receptor coactivator proteins mediate the stimulatory effects on gene transcription brought about by nuclear receptors, which comprise all steroid receptors. Using in situ hybridization we have examined the neuroanatomical distribution of the messenger RNAs (mRNAs) for two functionally distinct splice variants of Steroid Receptor Coactivator 1 (SRC-1/NCoA-1) and of Steroid Receptor Coactivator 2 (SRC-2/NCoA-2/GRIP-1/TIF-2). Transcripts encoding these coactivators show highly differential expression patterns. SRC-2 mRNA is expressed at very low levels in brain, but shows expression in the anterior pituitary. SRC-la and le mRNA are expressed in many brain areas, including hippocampus, amygdala, hypothalamus, basal ganglia, and isocortex. Striking differences between SRC-1a and le expression were observed in several brain nuclei. Relative levels of SRC-1a mRNA were much higher in anterior pituitary, and the arcuate, paraventricular and ventromedial nucleus of the hypothalamus, the locus coeruleus and the trigeminal motor nucleus, all important targets of steroid hormones in the brain. SRC-le mRNA showed modest elevation of relative expression in the caudal nucleus accumbens (shell), basolateral amygdala, and some thalamic nuclei. The differential and uneven neuroanatomical distribution of these coactivators may underlie diversity and cell-specificity of steroid receptor mediated signals in the brain.