放松素调节雌激素在子宫肌中的基因组作用和生物效应
Sudeshna Tripathy1,2,3, Anusha Nagari1,4, Shu-Ping Chiu1
1Laboratory of Signaling and Gene Regulation, Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
放松素 (Rln) 激素通过降低雌激素受体α (ERα) 活性来调节子宫中的雌激素 (E2) 作用. 这种相互作用影响基因表达和肌肉细胞收缩,揭示了一个新的信号通路.
科学领域:
- 生殖内分泌学 生殖内分泌学
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 雌激素 (E2) 和放松素 (Rln) 是女性生殖道中的关键激素.
- 由RXFP1介导的RLN作用可以通过雌激素受体α (ERα) 通过E2信号调节.
- 肌体内E2和Rln之间的相互作用是复杂的,有些作用是协同作用的,有些则是对抗作用的.
研究的目的:
- 阐明分子和基因组机制,规范E2和Rln之间的功能相互作用.
- 研究Rln如何影响E2在子宫光滑肌细胞中的基因组作用和生物效应.
主要方法:
- 使用了经过卵巢切除的雌性小鼠模型.
- 采用了表达野生型或突变型ERα的永生化人类肌肉细胞 (hTERT-HM-ERα).
- 分析了ERα酸化,基因组结合,转录组变化和肌肉细胞收缩.
主要成果:
- 在血清118 (S118) 中,Rln降低了E2依赖的ERα酸化.
- Rln减少了E2-依赖的ERα在整个基因组中的结合,改变了基因表达.
- 对于Rln对ERα酸化的抑制作用,需要核酸酶DUSP1和DUSP5.5.
- Rln联合治疗抑制了E2依赖的肌肉细胞收缩.
结论:
- Rln与E2/ERα信号传输,融合膜和核通路进行集成.
- Rln调节了E2的基因组作用和生理效应.
- 通过Rln/RXFP1和E2/ERα交声识别了一种新的信号通路,通过Rln/RXFP1和E2/ERα交声控制肌肉功能.
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