补偿机制维持了小鼠缺乏关键的雄激素生物合成酶的雄激素生产
Ben M Lawrence1,2, Liza O'Donnell3, Anne-Louise Gannon1
1College of Engineering, Science and Environment, The University of Newcastle, Callaghan, New South Wales, Australia.
概括
缺乏主要激素生产酶 (HSD17B3) 的雄性小鼠由于补偿性雄激素通路而保持生育能力. 这些替代途径,包括增加的SRD5A2活性和额外腺11-基托雄激素的产生,保持必要的激素水平.
科学领域:
- 内分泌学 在内分泌学.
- 生殖生物学 生殖生物学
- 生物化学 生物化学
背景情况:
- 和二 (DHT) 对于男性发育和生育能力至关重要.
- 正规的雄激素生产途径依赖于丸中的HSD17B3.
- Hsd17b3淘汰赛小鼠表现出生育能力,这表明了替代的雄激素生产机制.
研究的目的:
- 研究通过5α-减少酶 (SRD5A) 的替代DHT生产途径在Hsd17b3淘汰赛小鼠中的贡献.
- 检查正规和替代雄激素生产途径之间的相互作用.
- 确定在没有HSD17B3.3的情况下维持雄激素生物活性的补偿机制.
主要方法:
- 药理上抑制SRD5A活动.
- 在Hsd17b3淘汰赛小鼠中,Srd5a1的遗传移除.
- 分析循环和肠道内的雄激素,LH水平和类固醇酶表达.
主要成果:
- 任何一种途径的干扰都能维持男性的生育能力和生殖道的发育.
- 循环的替代途径类固醇在Hsd17b3KO小鼠中增加,但在SRD5A1抑制下降.
- 在Hsd17b3缺乏的情况下,丸Srd5a2表达显著增加,并且观察到循环11-keto-DHT的升高.
结论:
- 多种内和外腺机制弥补了 kanonical HSD17B3 途径的缺失.
- 这些补偿通路,包括SRD5A2上调和额外腺11-基因原体的产生,维持和DHT水平.
- 这些机制共同支持男性的发育和生育能力,尽管HSD17B3缺乏.
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