Mammalian target of rapamycin (mTOR): a central regulator of male fertility?
Mammalian target of rapamycin (mTOR): a central regulator of male fertility?
复制标题
哺乳动物雷帕霉素靶标(MTOR)：男性生育的中枢调节因子？
DOI：
10.1080/10409238.2017.1279120
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发表时间：
2017-06
影响因子：
6.5
通讯作者：
Alves MG
中科院分区：
文献类型：
--
作者：
Jesus TT;Oliveira PF;Sousa M;Cheng CY;Alves MG
哺乳动物雷帕霉素靶标(MTOR)是细胞代谢表型的中枢调节因子，几乎参与细胞功能的方方面面。它不仅整合了营养和能量感知途径，还整合了肌动蛋白细胞骨架组织，以响应包括生长因子和细胞能量水平在内的环境线索。这些事件是精子发生的关键，并决定了雄性的生殖潜力。然而，mTOR信号在男性生殖系统中作用的分子机制仍然存在争议。在这里，我们综述了目前关于mTOR在睾丸和睾丸细胞中介导的生理和分子事件的知识。近年来，mTOR抑制已被探索为开发新的治疗方法来治疗癌症、心血管疾病、自身免疫和代谢紊乱的主要策略。然而，mTOR失调和对男性生殖潜能的抑制的生理后果仍然不完全清楚。令人信服的证据表明，mTOR是男性生育能力的上升调节因子，更好地了解这种非典型蛋白激酶在睾丸中的协调作用将为其在其他组织/器官中的生物学意义提供有洞察力的信息。我们还讨论了为什么新一代旨在用于临床的mTOR抑制剂可能还需要包括对男性生殖系统影响的综合观点。
Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermato-genesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system.