Experssion and role of EGF,TGFalpha-EGF receptors autocrine mechanism in human fallopian tube

输卵管是早期胚胎发育的重要微环境，在早期胚胎发育中起重要作用。我们已经报道了表皮生长因子（EGF）和转化生长因子（TGF）α存在于人输卵管上皮中，参与早期胚胎发育。在这项研究中，我们已经表明，这些因子表达在输卵管上皮细胞特异性的月经周期阶段：其量成比例的血清雌二醇水平。此外，我们还研究了雌激素是否局部诱导这些因子。绝经后妇女的表皮生长因子受体及其配体的基因表达显着增加，在管上皮细胞。雌激素对培养的输卵管细胞也有类似的作用。这些数据表明雌激素在体内和体外直接诱导人输卵管上皮细胞的EGF、TGF α/EGF受体自分泌机制。 ...更多信息 雌激素诱导的自分泌机制。众所周知，子宫内膜上皮细胞对雌激素有反应性增殖，雌激素也会使输卵管上皮细胞增殖。我们测试了局部自分泌机制是否介导了雌激素诱导的小管上皮细胞生长。如果该机制介导雌激素作用，那么自分泌机制的阻断应该抑制雌激素诱导的细胞生长。抗EGF和抗EGF受体单克隆中和抗体可显著抑制雌激素诱导的输卵管上皮细胞生长。然而，抗TGF α抗体未能显示出该效果。EGF能恢复抗EGF对输卵管上皮细胞的生长抑制作用，而TGF α不能恢复抗EGF对输卵管上皮细胞的生长抑制作用。EGF和TGF α在早期胚胎发育中起作用，同时，局部自分泌机制在介导雌激素诱导的细胞生长中起重要作用。少

Fallopian tube represents an important microenvironment for an early embryo, it has a role in early embryo development. We have reported that epidermal growth factor (EGF) and transforming growth factor (TGF) alpha are present in human fallopian tube epithelium that are involved in early embryo development. In this study, we have shown that these factors are expressed in tubal epithelial cells specifically to the menstrual cycle stages : their amounts were in proportion to the serum estradiol levels. Furthermore, we examined if estrogen induces these factors locally. Estradiol treatment of postmenopausal women significantly increased the gene expression of EGF receptors and its ligands in tube epithelial cells. Estrogen also exhibited a similar effect on the cultured tubal cells. These data suggested that estrogen directly induces the EGF,TGFalpha/EGF receptor autocrine mechanism in human fallopian tube epithelial cells both in vivo and in vitro.We next examined the biological signific … More ance of estrogen inducible autocrine mechanism. It is well known that the endometrial epithelium proliferates in response to estrogen, and estrogen also proliferated fallopian tube epithelium. We tested if the local autocrine mechanism mediates the estrogen-induced tube epithelial cell growth. If the mechanism mediates the estrogen action, then the blockage of the autocrine mechanism should suppress the estrogen-induced cell growth. As expectedly, anti-EGF and -EGF receptor monoclonal neutralizing antibodies significantly inhibited the estrogen induced tubal cell growth in vitro. However, anti-TGFalpha antibody failed to show the effect. The data were confirmed by the fact that EGF but not TGFalpha could restore the growth-inhibition by anti-EGF.All these results indicate that there present a EGF and TGFalpha autocrine mechanism in human fallopian tube epithelial cells. EGF and TGFalpha play a role in early embryo development, and, at a same time, the local autocrine mechanism is important in mediating the estrogen induced cell growth. Less