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血小板衍生生长因子(PDGF)、表皮生长因子(EGF)以及人子宫内膜组织中的EGF和PDGFβ受体:定位与体外作用

Platelet-derived growth factor (PDGF), epidermal growth factor (EGF), and EGF and PDGF beta-receptors in human endometrial tissue: localization and in vitro action.

作者信息

Chegini N, Rossi M J, Masterson B J

机构信息

Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville 32610.

出版信息

Endocrinology. 1992 Apr;130(4):2373-85. doi: 10.1210/endo.130.4.1312455.

DOI:10.1210/endo.130.4.1312455
PMID:1312455
Abstract

Human endometrial tissue and primary stromal cell culture contain immunoreactive epidermal growth factor (EGF), platelet-derived growth factor (PDGF)-AB as well as EGF and PDGF-beta receptors. The immunostaining for EGF, EGF receptor, and PDGF beta-receptor were associated with endometrial luminal and glandular epithelial and stromal cells, whereas only the stromal cells contain immunoreactive PDGF-AB. The immunostaining intensity of EGF, EGF receptor, and PDGF-AB was similar in both phases of the menstrual cycle, whereas, PDGF-beta receptor immunostaining was highest in proliferative phase and considerably reduced, particularly in luminal and glandular epithelial cells in the secretory phase. In addition primary stromal cell cultures express EGF, PDGF-AB, and contain EGF and PDGF-beta receptors, and very low levels of PDGF-alpha receptor. 3H-Thymidine incorporation indicate that after 48 h of incubation in serum-free medium approximately 75-80% of stromal cells are quiescent. Incubation of quiescent stromal cells with 10% fetal bovine serum stimulate 3H-thymidine incorporation in a time-dependent manner reaching maximal after 30-48 h, with a doubling time of 38.2 h. EGF (1.5-15 ng/ml) stimulates 3H-thymidine incorporation by quiescent stromal cells (P less than 0.001). This effect was significantly reduced at concentrations above 15 ng/ml (P less than 0.005). PDGF-AB (3-10 ng/ml) and PDGF-BB (0.5-10 ng/ml) also stimulate 3H-thymidine incorporation in quiescent stromal cells compared to controls (P less than 0.005). The action of EGF (15 ng/ml) and PDGF-AB (10 ng/ml) was time dependent, reaching maximal after 36 and 48 h of incubation (P less than 0.002). Addition of PDGF-AB (10 ng/ml) to EGF (15 ng/ml) significantly enhanced the action of EGF or PDGF-AB used individually (P less than 0.001). 17 beta-estradiol or progesterone at 1 microM did not stimulate 3H-thymidine incorporation, although they were stimulatory in combination (P less than 0.001), they did not alter the action of EGF or PDGF when added in combination. These observations provide further evidence that human endometrial tissue contains specific immunoreactive EGF receptors. It also demonstrates the presence of immunoreactive EGF, PDGF-AB, and PDGF-beta receptors in endometrial tissue as well as stromal cells in primary culture. Both EGF and PDGF are mitogenic for endometrial stromal cells, suggesting an autocrine/paracrine role in modulation of endometrial cell growth and differentiation.

摘要

人子宫内膜组织和原代基质细胞培养物中含有免疫反应性表皮生长因子(EGF)、血小板衍生生长因子(PDGF)-AB以及EGF和PDGF-β受体。EGF、EGF受体和PDGF-β受体的免疫染色与子宫内膜腔面和腺上皮及基质细胞相关,而只有基质细胞含有免疫反应性PDGF-AB。EGF、EGF受体和PDGF-AB的免疫染色强度在月经周期的两个阶段相似,而PDGF-β受体免疫染色在增殖期最高,在分泌期显著降低,尤其是在腔面和腺上皮细胞中。此外,原代基质细胞培养物表达EGF、PDGF-AB,并含有EGF和PDGF-β受体以及极低水平的PDGF-α受体。3H-胸苷掺入表明,在无血清培养基中孵育48小时后,约75-80%的基质细胞处于静止状态。用10%胎牛血清孵育静止的基质细胞以时间依赖性方式刺激3H-胸苷掺入,在30-48小时后达到最大值,倍增时间为38.2小时。EGF(1.5-15 ng/ml)刺激静止的基质细胞掺入3H-胸苷(P<0.001)。在浓度高于15 ng/ml时,这种作用显著降低(P<0.005)。与对照组相比,PDGF-AB(3-10 ng/ml)和PDGF-BB(0.5-10 ng/ml)也刺激静止的基质细胞掺入3H-胸苷(P<0.005)。EGF(15 ng/ml)和PDGF-AB(10 ng/ml)的作用是时间依赖性的,在孵育36和48小时后达到最大值(P<0.002)。将PDGF-AB(10 ng/ml)添加到EGF(15 ng/ml)中可显著增强单独使用EGF或PDGF-AB的作用(P<0.001)。1 μM的17β-雌二醇或孕酮不刺激3H-胸苷掺入,尽管它们联合使用时有刺激作用(P<0.001),但联合添加时它们不改变EGF或PDGF的作用。这些观察结果进一步证明人子宫内膜组织含有特异性免疫反应性EGF受体。它还证明了子宫内膜组织以及原代培养的基质细胞中存在免疫反应性EGF、PDGF-AB和PDGF-β受体。EGF和PDGF对子宫内膜基质细胞均有促有丝分裂作用,提示在调节子宫内膜细胞生长和分化中起自分泌/旁分泌作用。

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