Odet Fanny, Guyot Romain, Leduque Patrick, Le Magueresse-Battistoni Brigitte
Institut National de la Santé et de la Recherche Médicale, Unité 329, Hopital Debrousse, 69322 Lyon Cedex 05, France.
Endocrinology. 2004 Mar;145(3):1481-9. doi: 10.1210/en.2003-0955. Epub 2003 Nov 26.
Plasminogen activators (PAs) and their inhibitors (PAIs) are predicted to be involved in the restructuring events that characterize the testis throughout development. We here demonstrate that PAI-3 or protein C (PC) inhibitor (PCI) was expressed in a sexually dimorphic fashion during mouse gonad genesis, whereas PAI-1 and -2 exhibited no sex differences. PCI transcripts accumulated rapidly in the male gonad, from 12.5 d postcoitum onward. Western blot and immunohistochemistry analyses confirmed that male, but not female, fetal gonads produced PCI, and that Leydig cells are the site of PCI synthesis. The occurrence of testicular target proteases for PCI, i.e. PC and urokinase- and tissue-type PA, was further tracked using RT-PCR, plasminogen zymography, and/or immunohistochemistry. PC and tissue-type PA showed no variation between sexes. By contrast, urokinase-type PA and its receptor (uPAR; which dictates the site and extent of proteolysis) exhibited sex differences from 13.5-14.5 d postcoitum. At that time, uPAR expression was restricted to Leydig cells. At earlier ages, uPAR was uniformly and widely distributed in the gonads of both sexes. In adult testes, PCI and uPAR immunoreactivities were also present in Leydig cells. In addition, PCI, PC, and uPAR had a germinal origin. Collectively, these results support the hypothesis that PCI may contribute to proteolysis equilibrium within the testis by acting in tandem with urokinase in Leydig cells and with PC and/or urokinase in spermatogenic cells. It will be important to determine how this role is linked to the phenotype of sterility reported elsewhere in male mice with pci deleted.
纤溶酶原激活剂（PAs）及其抑制剂（PAIs）被认为参与了睾丸在整个发育过程中的重塑事件。我们在此证明，PAI-3或蛋白C（PC）抑制剂（PCI）在小鼠性腺发生过程中以性别二态性方式表达，而PAI-1和PAI-2没有性别差异。PCI转录本在雄性性腺中从交配后12.5天开始迅速积累。蛋白质印迹和免疫组织化学分析证实，雄性而非雌性胎儿性腺产生PCI，并且睾丸间质细胞是PCI合成的部位。使用逆转录聚合酶链反应（RT-PCR）、纤溶酶原酶谱分析和/或免疫组织化学进一步追踪了PCI的睾丸靶蛋白酶，即PC、尿激酶型和组织型PA的存在情况。PC和组织型PA在两性之间没有差异。相比之下，尿激酶型PA及其受体（uPAR；它决定了蛋白水解的部位和程度）在交配后13.5 - 14.5天表现出性别差异。在那个时候，uPAR的表达仅限于睾丸间质细胞。在更早的年龄，uPAR在两性的性腺中均匀且广泛分布。在成年睾丸中，PCI和uPAR免疫反应性也存在于睾丸间质细胞中。此外，PCI、PC和uPAR起源于生殖细胞。总的来说，这些结果支持了这样一种假设，即PCI可能通过与睾丸间质细胞中的尿激酶以及生精细胞中的PC和/或尿激酶协同作用，有助于维持睾丸内的蛋白水解平衡。确定这种作用如何与其他地方报道的pci缺失雄性小鼠的不育表型相关联将是很重要的。
