Wulff C, Wilson H, Largue P, Duncan W C, Armstrong D G, Fraser H M
Medical Research Council, Human Reproductive Sciences Unit and Department of Obstetrics and Gynecology, Edinburgh, United Kingdom.
J Clin Endocrinol Metab. 2000 Nov;85(11):4302-9. doi: 10.1210/jcem.85.11.6942.
In the menstrual cycle, extensive angiogenesis accompanies luteinization. During luteolysis, endothelial cells die, whereas in a conceptual cycle, the corpus luteum (CL) persists, and endothelial cell survival is extended. A main stimulator for angiogenesis is vascular endothelial growth factor (VEGF), while the angiopoietins (Ang-1 and Ang-2) may be important modulators. The aim of this study was to investigate the localization of Ang-1, Ang-2, their common receptor Tie-2, and VEGF messenger ribonucleic acid (mRNA) at the different stages of the functional luteal phase and after rescue by hCG. Ang-1 mRNA was uniformly expressed at a low level throughout the CL. The signal was highest during the early luteal phase. In contrast, Ang-2 mRNA expression was localized strongly to individual granulosa and thecal luteal and endothelial cells. Administration of hCG was associated with an increase in the Ang-2 mRNA area of expression and grain density in individual luteal and endothelial cells. The Tie-2 receptor mRNA was localized in endothelial cells, and the area of expression was highest during the early luteal phase and during luteal rescue. VEGF mRNA was found exclusively in granulosa luteal cells, and the area of expression was highest in corpora lutea during simulated pregnancy. These results begin to characterize the molecular regulation of the divergent processes involved in luteal angiogenesis during luteinization, luteolysis, and rescue in the human and imply that the angiopoietins are involved during the initial angiogenic phase and in luteal rescue.
在月经周期中,广泛的血管生成伴随着黄体化过程。在黄体溶解过程中,内皮细胞死亡,而在妊娠周期中,黄体持续存在,内皮细胞存活时间延长。血管生成的主要刺激因子是血管内皮生长因子(VEGF),而血管生成素(Ang-1和Ang-2)可能是重要的调节因子。本研究的目的是调查Ang-1、Ang-2、它们的共同受体Tie-2以及VEGF信使核糖核酸(mRNA)在功能性黄体期不同阶段以及人绒毛膜促性腺激素(hCG)挽救后的定位情况。Ang-1 mRNA在整个黄体中均呈低水平均匀表达。信号在黄体早期最高。相比之下,Ang-2 mRNA表达强烈定位于单个颗粒细胞、黄体膜细胞和内皮细胞。给予hCG与单个黄体和内皮细胞中Ang-2 mRNA表达面积及颗粒密度增加有关。Tie-2受体mRNA定位于内皮细胞,表达面积在黄体早期和黄体挽救期间最高。VEGF mRNA仅在黄体颗粒细胞中发现,在模拟妊娠期间黄体中的表达面积最高。这些结果开始描绘出人类黄体化、黄体溶解和挽救过程中黄体血管生成不同过程的分子调控特征,并暗示血管生成素参与了初始血管生成阶段和黄体挽救过程。