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雄激素对小鼠前额叶皮质和中脑中的葡萄皮质皮质信号的限制性影响
Jorge Miguel Amaya1,2, Hetty C M Sips1,2, Eva M G Viho1,2
1Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, Netherlands.
Frontiers in endocrinology
|February 2, 2024
概括
雄激素受体 (AR) 信号调节特定大脑区域的葡萄糖皮质体反应,影响前额叶皮质和黑色物质中的基因表达. 这种相互作用不是占主导地位,而是发生在关键领域.
科学领域:
- 神经内分泌学神经内分泌学
- 分子精神病学分子精神病学
- 压力生理学 压力生理学
背景情况:
- 葡萄糖皮质类药物调解压力反应,而雄激素受体 (AR) 则影响它们在外围组织中的作用.
- 以前的研究表明,大脑基因表达对慢性压力的反应存在性别差异.
- 大脑中的雄激素和葡萄皮质激素之间的相互作用仍然不完全理解.
研究的目的:
- 调查雄激素信号是否调节葡萄糖皮质体受体 (GR) 在大脑中的向基因表达.
- 确定AR和GR共同定位和相互作用的特定大脑区域.
- 阐明雄激素和AR对抗作用在高皮质主义下的GR信号传递上的影响.
主要方法:
- 小鼠长期接受皮质激素,二激素,两者或皮质激素加上AR抗体恩扎胺的治疗.
- 对GR目标基因的基因表达进行了比较,这些基因表达在AR和GR共同表达的大脑区域 (前额皮质,下丘脑,海马体,VTA,黑色物质).
- 对特定基因表达水平进行了定量分析.
主要成果:
- 素信号调节的葡萄糖皮质体效应主要发生在前额皮质和黑色物质中.
- 二和皮质显示出前额皮层中Sgk1和Tsc22d3的独立和反向调节.
- 在前额叶皮层和黑色物质中的Fkbp5/Sgk1表达中,AR对抗与酶胺减弱的皮质激素诱导的Fkbp5表达.
- 在黑色物质中,AR对抗性增加了多巴胺基系统基因 (Th,Slc18a1).
结论:
- 雄激素对大脑中的葡萄皮质激素信号的影响是特定区域的,发生在前额叶皮质和黑色物质中.
- 这种调节在高皮质水平下并不占主导地位,但在这些关键领域是显著的.
- 雄激素信号影响黑色物质中的多巴胺基系统,这表明了更广泛的神经生物学影响.
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