EXTRACELLULAR MATRIX PRODUCTION BY UTERINE FIBROIDS

子宫平滑肌瘤，或称纤维瘤，是最常见的盆腔肿瘤， 妇女 这些平滑肌细胞肿瘤与以下症状有关， 包括骨盆疼痛或压迫、月经过多出血 不孕和自然流产。 平滑肌瘤似乎 雌激素/孕激素依赖，但目前尚不清楚这些卵巢 类固醇调节它们的生长。 尽管这些肿瘤可以 它们生长迅速，但有丝分裂活性很低。 纤维瘤的特征在于过量的细胞外基质。 拟议的研究重点是细胞外基质的调控 卵巢类固醇在平滑肌瘤和正常子宫肌层中的产生 以及自分泌生长调节剂，转化生长因子β和 甲状旁腺相关肽 这项建议的具体目标是： 1.为了比较人子宫平滑肌瘤和子宫肌层中a） 细胞外基质蛋白I型胶原、III型胶原和 纤连蛋白，和B）基质降解酶溶基质酶，和 胶原酶 2.为了确定这些细胞外基质的表达是否 蛋白质和基质降解酶在平滑肌瘤和子宫肌层， 由雌激素和/或孕酮调节。 3.为了确定a）平滑肌瘤是否产生更高量的PTHrP， TGF-B比正常子宫肌层，以及B）PTHrP和TGF-B是否调节 产生细胞外基质蛋白或基质降解酶。 这些研究应提供新的信息， 正常子宫肌层和子宫内膜中的细胞外基质产生 平滑肌瘤 生产过剩或降解减少 纤维瘤的细胞外基质蛋白可能占其 增长或“成长”。 一个或多个这些基因的过度表达 基质蛋白的平滑肌瘤，增强反应的影响， 雌激素/孕激素，或自分泌调节剂的产生增加 如PTHrP或TGF-B可能是其中的一些机制 基质过度积累。 这些发现可能有助于 这些常见肿瘤的临床治疗进展。

Uterine leiomyomas, or fibroids, are the most common pelvic tumors in women. These smooth muscle cell tumors are associated with symptoms that include pelvic pain or pressure, excessive menstrual bleeding, infertility and spontaneous abortion. Leiomyomas appear to be estrogen/progesterone dependent but it is not clear how these ovarian steroids regulate their growth. Despite the fact that these tumors can grow quite rapidly, they display very low rates of mitotic activity. Fibroids are characterized by excessive amounts of extra-cellular matrix. The proposed research focuses on the regulation of extra-cellular matrix production in leiomyomas and normal myometrium by the ovarian steroids and the autocrine growth regulators, transforming growth factor-beta and parathyroid hormone-related peptide. The specific aims of this proposal are: 1. To compare human uterine leiomyoma and myometrial expression of a) the extra-cellular matrix proteins collagen Type I, collagen Type III and fibronectin, and b) the matrix-degrading enzymes stromelysin and collagenase. 2. To determine whether expression of these extra-cellular matrix proteins and matrix-degrading enzymes in leiomyomas and myometrium is regulated by estrogen and/or progesterone. 3. To determine a) whether leiomyomas produce higher amounts of PTHrP and TGF-B than normal myometrium, and b) whether PTHrP and TGF-B regulate the production of extra-cellular matrix proteins or matrix-degrading enzymes. These studies should provide new information on the regulation of extra-cellular matrix production in both normal myometrium and leiomyomas. Overproduction or decreased degradation of certain extra-cellular matrix proteins by fibroids may account for much of their increase in size or "growth". Overexpression of one or more of these matrix proteins by leiomyomas, enhanced responsiveness to the effects of estrogen/progesterone, or increased production of autocrine regulators such as PTHrP or TGF-B may be some of the mechanisms responsible for this excessive accumulation of matrix. The findings may facilitate developments in the clinical management of these common tumors.