Trypsin is a multifunctional factor in spermatogenesis
Trypsin is a multifunctional factor in spermatogenesis
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DOI：
10.1073/pnas.0907631106
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发表时间：
2009-12-08
影响因子：
11.1
通讯作者：
Miura, Takeshi
中科院分区：
文献类型：
--
作者：
Miura, Chiemi;Ohta, Takashi;Miura, Takeshi
众所周知，胰酶是一种胰酶，通常分泌到肠道中消化蛋白质。然而，我们在目前的研究中表明，胰酶也是控制精子发生的关键因素。硬骨鱼中的孕激素，17α，20β-二羟基-4-孕烯-3-酮(DHP)，是精子发生途径的重要组成部分，特别是在第一次减数分裂的起始阶段。在研究孕激素刺激精子发生的机制的过程中，我们发现DHP处理可上调鳗鱼睾丸中的胰蛋白酶原。胰蛋白酶原在精原细胞周围的支持细胞、精子细胞膜和精子膜中表达。利用鳗鱼睾丸体外培养系统，我们进一步分析了胰酶在精子发生中的作用。用特异性抗体或丝氨酸蛋白酶抑制剂抑制胰酶可抑制DHP诱导的精子发生。低剂量的胰酶可诱导生殖细胞DNA合成和Spo11的表达，Spo11是减数分裂的分子标志物。相比之下，较高剂量的胰酶部分诱导了精子生成。此外，在精子膜中可以检测到胰蛋白酶，并发现与鱼类受精有关。因此，我们的研究结果表明，胰酶和/或类胰蛋白酶是精子发生过程中一种必不可少的多功能因子。
Trypsin is well known as a pancreatic enzyme that is typically secreted into the intestine to digest proteins. We show in our current study, however, that trypsin is also a key factor in the control of spermatogenesis. A progestin in teleost fish, 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (DHP), is an essential component of the spermatogenesis pathway, particularly during the initiation of the first meiotic division. In the course of our investigations into the mechanisms underlying progestin-stimulated spermatogenesis, we identified that eel trypsinogen is upregulated in eel testis by DHP treatment. Trypsinogen is expressed in the Sertoli cells surrounding spermatogonia and in the membranes of spermatids and spermatozoa. Using an in vitro eel testicular culture system, we further analyzed the roles of trypsin in spermatogenesis. The inhibition of trypsin using specific antibodies or serine protease inhibitors was found to compromise DHP-induced spermatogenesis. A low dose of trypsin induces DNA synthesis and the expression of Spo11, a molecular marker of meiosis, in germ cells. By comparison, a higher dose of trypsin partially induced spermiogenesis. Furthermore, trypsin was detectable in the membranes of the spermatozoa and found to be associated with fertilization in fish. Our results thus demonstrate that trypsin and/or a trypsin-like protease is an essential and multifunctional factor in spermatogenesis.