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Revisiting the action of steroids and triterpenoids on the human sperm Ca2+ channel CatSper.
Molecular Human Reproduction ( IF 3.6 ) Pub Date : 2020-09-14 , DOI: 10.1093/molehr/gaaa062
Anders Rehfeld 1, 2, 3
Affiliation  

The sperm-specific Ca2+ channel CatSper (cation channel of sperm) is vital for male fertility. Contradictory findings have been published on the regulation of human CatSper by the endogenous steroids estradiol, testosterone and hydrocortisone, as well as the plant triterpenoids, lupeol and pristimerin. The aim of this study was to elucidate this controversy by investigating the action of these steroids and plant triterpenoids on human CatSper using population-based Ca2+-fluorimetric measurements, the specific CatSper-inhibitor RU1968 and a functional test assessing the CatSper-dependent penetration of human sperm cells into methylcellulose. Estradiol, testosterone and hydrocortisone were found to induce Ca2+-signals in human sperm cells with EC50 values in the lower μM range. By employing the specific CatSper-inhibitor RU1968, all three steroids were shown to induce Ca2+-signals through an action on CatSper, similar to progesterone. The steroids were found to dose-dependently inhibit subsequent progesterone-induced Ca2+-signals with IC50 values in the lower μM range. Additionally, the three steroids were found to significantly increase the penetration of human sperm cells into methylcellulose, similar to the effect of progesterone. The two plant triterpenoids, lupeol and pristimerin, were unable to inhibit progesterone-induced Ca2+-signals, whereas the CatSper-inhibitor RU1968 strongly inhibited progesterone-induced Ca2+-signals. In conclusion, this study supports the claim that the steroids estradiol, testosterone and hydrocortisone act agonistically on CatSper in human sperm cells, thereby mimicking the effect of progesterone, and that lupeol and pristimerin do not act as inhibitors of human CatSper.

中文翻译:

重新审视类固醇和三萜类化合物对人类精子 Ca2+ 通道 CatSper 的作用。

精子特异性 Ca 2+通道 CatSper(精子的阳离子通道)对男性生育能力至关重要。内源性类固醇雌二醇、睾酮和氢化可的松以及植物三萜类化合物、羽扇豆醇和普利司默林对人类 CatSper 的调节发表了相互矛盾的研究结果。这项研究的目的是通过人口调查这些类固醇和植物三萜类化合物对人类的CatSper的行动,以阐明这种争议-基于钙2+ -fluorimetric测量,具体CatSper -抑制剂RU1968和功能测试评估CatSper依赖渗透人类精子细胞转化为甲基纤维素。发现雌二醇、睾酮和氢化可的松可诱导 Ca 2+-EC 50值在较低 μM 范围内的人类精子细胞中的信号。通过使用特定的 CatSper -抑制剂 RU1968,所有三种类固醇都显示通过对 CatSper 的作用诱导 Ca 2+ -信号,类似于孕酮。发现类固醇以剂量依赖性方式抑制随后的孕酮诱导的 Ca 2+信号,IC 50值在较低 μM 范围内。此外,发现这三种类固醇可显着增加人类精子细胞对甲基纤维素的渗透,类似于黄体酮的作用。两种植物三萜类化合物羽扇豆醇和 pristimerin 无法抑制孕酮诱导的 Ca 2+ -信号,而 CatSper -抑制剂 RU1968 强烈抑制孕酮诱导的 Ca 2+信号。总之,这项研究支持以下说法:类固醇雌二醇、睾酮和氢化可的松对人类精子细胞中的 CatSper 有激动作用,从而模拟孕酮的作用,并且羽扇豆醇和 pristimerin 不会作为人类 CatSper 的抑制剂。
更新日期:2020-11-09
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