在不同阴茎细胞群中调节AR和SOX9表达中的Kctd13的作用
Carolina J Jorgez1,2,3, Ahmed Chahdi2,3, Hunter Flores1
1Scott Department of Urology, Baylor College of Medicine, Houston, Texas, USA.
Andrology
|January 31, 2025
概括
在Kctd13淘汰赛小鼠中恢复雄激素受体 (AR) 和SOX9水平,挽救了微阴茎和提高了生育能力. KCTD13调节AR无处不在,影响阴茎发育.
科学领域:
- 发育生物学是发展生物学.
- 分子内分泌学分子内分泌学
- 遗传学 是一个遗传学.
背景情况:
- 微阴茎,通常是由减少的雄激素作用引起的,具有显著的身体和心理影响.
- 由于较低的雄激素受体 (AR) 和SOX9水平,Kctd13-Knockout (Kctd13-KO) 小鼠表现出微阴茎,密码性和生育问题.
研究的目的:
- 研究AR和SOX9在阴茎发育中的作用.
- 了解KCTD13在微阴茎的背景下影响AR和SOX9水平的机制.
主要方法:
- 产生了AR (AR+) 或SOX9 (SOX9+) 条件表达的Kctd13-KO小鼠.
- 在Kctd13-KO,AR+,SOX9+和野生型 (WT) 小鼠中评估阴茎形态,生育能力和AR/SOX9无处不在.
- 研究了KCTD13对HEK293细胞中AR泛基化的影响,包括蛋白酶体通路和STUB1.1的作用.
主要成果:
- AR+和SOX9+小鼠的阴茎长度恢复,与WT小鼠相当,表明微阴茎表型的逆转.
- 与Kctd13-KO小鼠相比,AR+和SOX9+小鼠的雄性泌尿器官交配突起和乳头长度/宽度显著改善.
- 宫外表达的KCTD13减少了AR泛化,这种过程由STUB1介导,并且依赖于蛋白酶体路径;KCTD13对SOX9泛化的影响很小.
结论:
- 在Kctd13-KO小鼠中恢复AR或SOX9水平有效地拯救了微阴茎表型并改善了生育能力.
- KCTD13通过调节STUB1与AR的结合来调节AR的泛化,从而影响阴茎的发育.
- 这项研究阐明了AR和SOX9信号通路和细胞类型在阴茎发育中的独特贡献.
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