Walker Cheryl L
The University of Texas M.D. Anderson Cancer Center, Department of Carcinogenesis, Smithville 78957, USA.
Recent Prog Horm Res. 2002;57:277-94. doi: 10.1210/rp.57.1.277.
Uterine leiomyomas are the most common gynecologic neoplasm in reproductive-age women. While it is clear that hormonal factors play a prominent role in this disease, how steroid hormones contribute to disease etiology or may be utilized as targets for intervention are currently areas of active scientific investigation. To study the impact of hormones on uterine leiomyomas, the Eker rat has been developed as an in vivolin vitro animal model system for these tumors. Spontaneous leiomyomas arise in intact Eker rats with a high frequency and leiomyoma-derived cell lines from these animals maintain the biochemical and physiological characteristics of the tumors from which they were obtained. Using this animal model system, it has been established that tumor development is absolutely dependent on steroid hormones and that sensitivity/responsiveness to estrogen is enhanced in tumors and tumor-derived cell lines. Modulation of hormonal milieu, such as that which naturally occurs during pregnancy, can effectively inhibit tumor development. The hormone responsiveness of these tumors makes them good candidates for hormonal therapy. Selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene hold promise as potential therapeutic agents for this disease. SERMs inhibit proliferation of leiomyoma-derived cell lines in vitro, repress the growth of these lines in nude mice, and, when administered over a 2- to 4-month course of treatment to Eker rats, reduce tumor incidence by more than 50%. In addition to endogenous hormones, xenoestrogens in our environment (e.g., phytoestrogens, organochlorine pesticides, pharmacologic compounds) are of potential concern with regards to their impact on this disease. These environmental estrogens have been shown to promote the growth of leiomyoma cells in vitro and in vivo. Further elucidation of the role of these and other hormonal and reproductive factors in the development of uterine leiomyoma will be invaluable for increasing our understanding of the etiology of this disease and developing new therapeutic strategies to help to reduce the negative impact of uterine leiomyomas on women's health.
子宫平滑肌瘤是育龄期女性最常见的妇科肿瘤。虽然激素因素在这种疾病中起着重要作用这一点很明确，但类固醇激素如何导致疾病病因或可作为干预靶点目前仍是科学研究的活跃领域。为了研究激素对子宫平滑肌瘤的影响，已开发出Eker大鼠作为这些肿瘤的体内/体外动物模型系统。完整的Eker大鼠中会高频自发产生平滑肌瘤，并且来自这些动物的平滑肌瘤衍生细胞系保留了其来源肿瘤的生化和生理特征。利用这个动物模型系统，已证实肿瘤的发展绝对依赖类固醇激素，并且肿瘤及肿瘤衍生细胞系对雌激素的敏感性/反应性增强。激素环境的调节，如孕期自然发生的调节，可有效抑制肿瘤发展。这些肿瘤的激素反应性使其成为激素治疗的良好候选对象。选择性雌激素受体调节剂（SERM）他莫昔芬和雷洛昔芬有望成为这种疾病的潜在治疗药物。SERM在体外可抑制平滑肌瘤衍生细胞系的增殖，在裸鼠中可抑制这些细胞系的生长，并且当对Eker大鼠进行2至4个月的疗程给药时，可使肿瘤发生率降低超过50%。除了内源性激素外，我们环境中的外源性雌激素（如植物雌激素、有机氯农药、药物化合物）对这种疾病的影响也值得关注。这些环境雌激素已被证明在体外和体内均可促进平滑肌瘤细胞的生长。进一步阐明这些及其他激素和生殖因素在子宫平滑肌瘤发展中的作用，对于增进我们对这种疾病病因的理解以及开发新的治疗策略以帮助减少子宫平滑肌瘤对女性健康的负面影响将具有重要价值。
