Liu K, Liu Y X, Hu Z Y, Zou R Y, Chen Y J, Mu X M, Ny T
Department of Medical Biochemistry and Biophysics, University of Umeå, Sweden.
Mol Cell Endocrinol. 1997 Oct 20;133(2):109-16. doi: 10.1016/s0303-7207(97)00152-4.
Proteolytic activity generated by the plasminogen activator (PA) system has been associated with many biological processes. Using a pregnant mare serum gonadotropin (PMSG)/human chorionic gonadotropin (hCG)-induced rhesus monkey corpus luteum (CL) model, we have studied how urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), and plasminogen activator inhibitor type 1 (PAI-1), are temporally expressed in CL of rhesus monkey at the luteotropic and luteolytic periods. Slot blot analysis and in situ hybridization were performed to analyze the expression and distribution of uPA and PAI-1 messenger RNA (mRNA). Fibrin overlay was used to detect uPA and tPA activities. We found that uPA is the dominating PA in luteotropic CL in the monkey. Abundant expression of PAI-1 mRNA was detected. The highest expression of uPA and PAI-1 mRNA was observed at the luteotropic period, while their expression decreased approximately 50% at early luteal regression defined by considerably decreased serum progesterone levels, and remained at very low levels at the late stage of luteal regression. We also observed an increased tPA activity at the time of luteal regression. Moreover, the exogenous tPA could inhibit the progesterone production in cultured luteal cells from 13-day-old monkey CL. We also used LH receptor mRNA expression as a mark for the luteal phases. A highly expressed, evenly distributed LH receptor mRNA was detected in CL during the luteotropic phase, while its expression decreased at day 13 coinciding with the reduction of progesterone production. We conclude that proteolysis mediated by uPA and regulated by PAI-1 may play a role in the luteal maintenance, while tPA may participate in the luteal regression in the rhesus monkey.
纤溶酶原激活物(PA)系统产生的蛋白水解活性与许多生物学过程相关。利用孕马血清促性腺激素(PMSG)/人绒毛膜促性腺激素(hCG)诱导的恒河猴黄体(CL)模型,我们研究了尿激酶型纤溶酶原激活物(uPA)、组织型纤溶酶原激活物(tPA)和纤溶酶原激活物抑制剂1型(PAI-1)在恒河猴黄体期和黄体溶解期的黄体(CL)中如何随时间表达。进行狭缝印迹分析和原位杂交以分析uPA和PAI-1信使核糖核酸(mRNA)的表达和分布。采用纤维蛋白覆盖法检测uPA和tPA活性。我们发现uPA是恒河猴黄体期黄体(CL)中占主导地位的PA。检测到PAI-1 mRNA的丰富表达。uPA和PAI-1 mRNA在黄体期表达最高,而在血清孕酮水平显著下降所定义的黄体早期退化时,它们的表达下降约50%,并在黄体退化后期维持在非常低的水平。我们还观察到在黄体退化时tPA活性增加。此外,外源性tPA可抑制来自13日龄恒河猴黄体(CL)的培养黄体细胞中的孕酮产生。我们还将促黄体生成素(LH)受体mRNA表达用作黄体期的标志。在黄体期,黄体(CL)中检测到高表达、均匀分布的LH受体mRNA,而其表达在第13天下降,与孕酮产生的减少一致。我们得出结论,由uPA介导并受PAI-1调节的蛋白水解作用可能在黄体维持中起作用,而tPA可能参与恒河猴的黄体退化。