Charlier T D, Ball G F, Balthazart J
University of Liège, Center for Cellular and Molecular Neurobiology, Research Group in Behavioral Neuroendocrinology, Liège, Belgium.
Neuroscience. 2006 Jul 21;140(4):1381-94. doi: 10.1016/j.neuroscience.2006.03.002. Epub 2006 May 2.
Analysis of nuclear receptor action on the eukaryotic genome highlights the importance of coactivators on gene transcription. The steroid receptor coactivator-1 in particular is the focus of an intense research and physiological or behavioral studies have confirmed that it plays a major role in the modulation of steroid and thyroid receptors activity. However, little is known about the regulation of steroid receptor coactivator-1 expression the brain. The goal of this study was to determine the potential factors modulating steroid receptor coactivator-1 synthesis in Japanese quail by quantification of its mRNA with real time quantitative polymerase chain reaction and of the corresponding protein via Western blotting. Contrary to previously published results from our laboratory [Charlier TD, Lakaye B, Ball GF, Balthazart J (2002) The steroid receptor coactivator SRC-1 exhibits high expression in steroid-sensitive brain areas regulating reproductive behaviors in the quail brain. Neuroendocrinology 76:297-315], we found here that sexually mature females had a higher concentration of steroid receptor coactivator-1 in the preoptic area/hypothalamus compared with males. Steroid receptor coactivator-1 expression in the male preoptic area/hypothalamus was up-regulated by testosterone and tended to be decreased by stress. We also identified a significant correlation between the time of the day and the expression of the coactivator in the optic lobes, hippocampus, telencephalon and hindbrain but the pattern of changes in expression as a function of the time of the day varied from one brain area to another. Together, these data support the idea that steroid receptor coactivator-1 is not constitutively expressed but rather is finely regulated by steroids, stress and possibly other unidentified factors.
对核受体作用于真核基因组的分析突出了共激活因子在基因转录中的重要性。特别是类固醇受体共激活因子-1成为了深入研究的焦点,生理学或行为学研究已证实它在调节类固醇和甲状腺受体活性方面发挥着主要作用。然而,关于大脑中类固醇受体共激活因子-1表达的调控却知之甚少。本研究的目的是通过实时定量聚合酶链反应对其mRNA进行定量,并通过蛋白质印迹法对相应蛋白质进行定量,以确定调节日本鹌鹑体内类固醇受体共激活因子-1合成的潜在因素。与我们实验室之前发表的结果[查理尔TD,拉凯B,鲍尔GF,巴尔萨扎特J(2002年)类固醇受体共激活因子SRC-1在调节鹌鹑大脑生殖行为的类固醇敏感脑区中高表达。神经内分泌学76:297 - 315]相反,我们在此发现,性成熟雌性的视前区/下丘脑类固醇受体共激活因子-1浓度高于雄性。雄性视前区/下丘脑的类固醇受体共激活因子-1表达受睾酮上调,且应激时有降低趋势。我们还发现一天中的时间与视叶、海马体、端脑和后脑中共激活因子的表达之间存在显著相关性,但不同脑区中表达随时间变化的模式各不相同。总之,这些数据支持这样一种观点,即类固醇受体共激活因子-1并非组成性表达,而是受到类固醇、应激以及可能其他未知因素的精细调节。