Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720
Proc Natl Acad Sci U S A. 2017 May 30;114(22):5743-5748. doi: 10.1073/pnas.1700367114. Epub 2017 May 15.
The calcium channel of sperm (CatSper) is essential for sperm hyperactivated motility and fertility. The steroid hormone progesterone activates CatSper of human sperm via binding to the serine hydrolase ABHD2. However, steroid specificity of ABHD2 has not been evaluated. Here, we explored whether steroid hormones to which human spermatozoa are exposed in the male and female genital tract influence CatSper activation via modulation of ABHD2. The results show that testosterone, estrogen, and hydrocortisone did not alter basal CatSper currents, whereas the neurosteroid pregnenolone sulfate exerted similar effects as progesterone, likely binding to the same site. However, physiological concentrations of testosterone and hydrocortisone inhibited CatSper activation by progesterone. Additionally, testosterone antagonized the effect of pregnenolone sulfate. We have also explored whether steroid-like molecules, such as the plant triterpenoids pristimerin and lupeol, affect sperm fertility. Interestingly, both compounds competed with progesterone and pregnenolone sulfate and significantly reduced CatSper activation by either steroid. Furthermore, pristimerin and lupeol considerably diminished hyperactivation of capacitated spermatozoa. These results indicate that () pregnenolone sulfate together with progesterone are the main steroids that activate CatSper and () pristimerin and lupeol can act as contraceptive compounds by averting sperm hyperactivation, thus preventing fertilization.
精子钙通道（CatSper）对于精子的超激活运动和生育能力至关重要。甾体激素孕酮通过与丝氨酸水解酶 ABHD2 结合来激活人精子的 CatSper。然而，ABHD2 的甾体特异性尚未得到评估。在这里，我们探讨了男性和女性生殖道中人类精子暴露的甾体激素是否通过调节 ABHD2 来影响 CatSper 的激活。结果表明，睾酮、雌酮和氢化可的松不会改变基础 CatSper 电流，而神经甾体孕烯醇酮硫酸盐与孕酮具有相似的作用，可能与相同的结合位点结合。然而，生理浓度的睾酮和氢化可的松抑制了孕酮对 CatSper 的激活作用。此外，睾酮拮抗了孕烯醇酮硫酸盐的作用。我们还探讨了甾体样分子，如植物三萜类化合物普瑞马林和羽扇豆醇，是否会影响精子的生育能力。有趣的是，这两种化合物都与孕酮和孕烯醇酮硫酸盐竞争，并显著降低了这两种甾体对 CatSper 的激活作用。此外，普瑞马林和羽扇豆醇大大减少了获能精子的超激活。这些结果表明：（）孕烯醇酮硫酸盐与孕酮一起是激活 CatSper 的主要甾体；（）普瑞马林和羽扇豆醇可以作为避孕药化合物，通过阻止精子超激活，从而防止受精。
