Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: Implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis
Ovarian steroid regulation of vascular endothelial growth factor in the human endometrium: Implications for angiogenesis during the menstrual cycle and in the pathogenesis of endometriosis
复制标题
DOI：
10.1210/jc.81.8.3112
复制
发表时间：
1996-08-01
影响因子：
5.8
通讯作者：
Taylor, RN
中科院分区：
文献类型：
--
作者：
Shifren, JL;Tseng, JF;Taylor, RN
人类子宫内膜在每个月经周期都经历一个复杂的血管和腺体增殖、分化和再生过程，为着床做准备。血管内皮生长因子（VEGF）是一种内皮细胞特异性的血管生成蛋白，在生理和病理性新生血管形成中发挥重要作用。为了研究VEGF是否可以调节人子宫内膜血管生成，我们在整个月经周期中检测了VEGF信使核糖核酸（mRNA）和蛋白质，并研究了生殖类固醇对离体人子宫内膜细胞中VEGF的调节。通过核糖核酸酶保护分析，VEGF mRNA相对于早期增殖期表达分别增加了1.6倍，2.0倍和3.6倍，在中期增殖，晚期增殖和分泌期子宫内膜。在组织学切片中，VEGF mRNA和蛋白定位于腺上皮细胞和周围间质中更广泛，分泌期子宫内膜中VEGF表达最高。与这些体内结果一致，用雌二醇（E（2））、醋酸甲羟孕酮（MPA）或E（2）+MPA处理分离的人子宫内膜细胞，VEGF mRNA表达分别比对照值显著增加3.1倍、2.8倍和4.7倍。VEGF对E（2）的反应迅速，在加入类固醇后1小时，VEGF mRNA的稳态水平最高达到85%。E（2）还引起分泌的VEGF蛋白增加46%，E（2）和MPA联合引起18%的增加。子宫内膜异位症（一种血管生成依赖性、雌激素敏感性疾病）中的VEGF表达与在位子宫内膜中所见的相似。中重度子宫内膜异位症患者的腹腔液VEGF浓度显著高于轻度子宫内膜异位症或无疾病的患者。因此，VEGF在人子宫内膜的生理和病理血管生成中可能是重要的，因为它是一种雌激素反应性血管生成因子，在整个月经周期中变化，并且在子宫内膜异位症女性中升高。
The human endometrium undergoes a complex process of vascular and glandular proliferation, differentiation, and regeneration with each menstrual cycle in preparation for implantation. Vascular endothelial growth factor (VEGF) is an endothelial cell-specific angiogenic protein that appears to play an important role in both physiological and pathological neovascularization. To investigate whether VEGF may regulate human endometrial angiogenesis, we examined VEGF messenger ribonucleic acid (mRNA) and protein throughout the menstrual cycle and studied the regulation of VEGF by reproductive steroids in isolated human endometrial cells. By ribonuclease protection analysis, VEGF mRNA increased relative to early proliferative phase expression by 1.6-, 2.0-, and 3.6-fold in midproliferative, late proliferative, and secretory endometrium, respectively. In histological sections, VEGF mRNA and protein were localized focally in glandular epithelial cells and more diffusely in surrounding stroma, with greatest VEGF expression in secretory endometrium. Consistent with these in vivo results, the treatment of isolated human endometrial cells with Estradiol (E(2)), medroxyprogesterone acetate (MPA), or E(2) plus MPA significantly increased VEGF mRNA expression over the control value by 3.1-, 2.8-, and 4.7-fold, respectively. The VEGF response to E(2) was rapid, with steady state levels of VEGF mRNA reaching 85% maximum 1 h after the addition of steroid. E(2) also caused a 46% increase in secreted VEGF protein, and the combination of E(2) and MPA caused an 18% increase, VEGF expression in endometriosis, an angiogenesis-dependent, estrogen-sensitive disease was similar to that seen in eutopic endometrium. Peritoneal fluid concentrations of VEGF were significantly higher in women with moderate to severe endometriosis than in women with minimal to mild endometriosis or no disease. VEGF, therefore, may be important in both physiological and pathological angiogenesis of human endometrium, as it is an estrogen-responsive angiogenic factor that varies throughout the menstrual cycle and is elevated in women with endometriosis.