Rossi M J, Chegini N, Masterson B J
Department of Obstetrics and Gynecology, University of Florida College of Medicine, Gainesville 32610.
Endocrinology. 1992 Mar;130(3):1716-27. doi: 10.1210/endo.130.3.1311246.
Immunohistochemical observations indicate that human myometrial smooth muscle cells express epidermal growth factor (EGF) and platelet-derived growth factor (PDGF)-AB and contain EGF and PDGF-beta receptors with no variation in intensity with phases of the menstrual cycle. Furthermore, immunofluorescent microscopic studies revealed that primary myometrial smooth muscle cell cultures also express EGF, PDGF-AB, and contain EGF and PDGF-beta, but not alpha-receptor. Incubation of subconfluent smooth muscle cells in serum-free medium leads to quiescence within 48 h as demonstrated by 3H-thymidine incorporation and labeling index. Exposure of quiescent cells to 10% fetal bovine serum stimulates resumption of DNA synthesis and proliferation in a time-dependent manner with a doubling time of 41.6 h. EGF (1.5-50 ng/ml) and PDGF-AB (1-10 ng/ml) in a dose- and time-dependent manner significantly stimulated 3H-thymidine incorporation by quiescent myometrial smooth muscle cells (P less than 0.05). Combinations of EGF (15 ng/ml) and PDGF-AB (10 ng/ml) significantly increased 3H-thymidine incorporation induced by either growth factor alone (P less than 0.05). PDGF-BB at 10 ng/ml also stimulated 3H-thymidine incorporation and its effect was similar to that induced by PDGF-AB at the same concentration. 17 beta-Estradiol (E2) at 1 microM inhibited 3H-thymidine incorporation by the smooth muscle cells (P less than 0.05). E2 also reduced the stimulatory effect of EGF (15 ng/ml) and PDGF (3 ng/ml). Progesterone at 1 microM either alone or in combination with E2 did not have any effect on 3H-thymidine incorporation or alter the mitogenic action of EGF and PDGF. The effect of EGF and PDGF on cell growth and 3H-thymidine incorporation by myometrial smooth muscle cells was independent of phases of the menstrual cycle. In summary, the results of present studies indicate that human myometrial tissue and myometrial smooth muscle cells in primary culture locally produce EGF and PDGF-AB and contain EGF and PDGF-beta, but not alpha-receptors. Moreover, the myometrial smooth muscle cells in culture respond to the mitogenic action of EGF and PDGF.
免疫组织化学观察表明，人子宫肌层平滑肌细胞表达表皮生长因子（EGF）和血小板衍生生长因子（PDGF）-AB，并含有EGF和PDGF-β受体，且其强度在月经周期各阶段无变化。此外，免疫荧光显微镜研究显示，原代子宫肌层平滑肌细胞培养物也表达EGF、PDGF-AB，并含有EGF和PDGF-β，但不含有α受体。在无血清培养基中培养亚汇合的平滑肌细胞，48小时内细胞进入静止期，这通过3H-胸腺嘧啶核苷掺入和标记指数得以证明。将静止细胞暴露于10%胎牛血清中，可刺激DNA合成恢复并以时间依赖性方式增殖，倍增时间为41.6小时。EGF（1.5 - 50 ng/ml）和PDGF-AB（1 - 10 ng/ml）以剂量和时间依赖性方式显著刺激静止的子宫肌层平滑肌细胞掺入3H-胸腺嘧啶核苷（P < 0.05）。EGF（15 ng/ml）和PDGF-AB（10 ng/ml）联合使用显著增加了单独一种生长因子诱导的3H-胸腺嘧啶核苷掺入量（P < 0.05）。10 ng/ml的PDGF-BB也刺激了3H-胸腺嘧啶核苷掺入，其作用与相同浓度的PDGF-AB诱导的作用相似。1 μM的17β-雌二醇（E2）抑制平滑肌细胞掺入3H-胸腺嘧啶核苷（P < 0.05）。E2还降低了EGF（15 ng/ml）和PDGF（3 ng/ml）的刺激作用。1 μM的孕酮单独或与E2联合使用对3H-胸腺嘧啶核苷掺入均无任何影响，也不改变EGF和PDGF的促有丝分裂作用。EGF和PDGF对子宫肌层平滑肌细胞生长和3H-胸腺嘧啶核苷掺入的作用与月经周期阶段无关。总之，本研究结果表明，人子宫肌层组织及原代培养的子宫肌层平滑肌细胞可局部产生EGF和PDGF-AB，并含有EGF和PDGF-β，但不含有α受体。此外，培养的子宫肌层平滑肌细胞对EGF和PDGF的促有丝分裂作用有反应。
