EXTRACELLULAR MATRIX PRODUCTION BY UTERINE FIBROIDS

子宫肌瘤，或肌瘤，是最常见的盆腔肿瘤 女人。这些平滑肌细胞肿瘤与以下症状有关 包括盆腔疼痛或压迫，月经过多， 不孕不育和自然流产。平滑肌瘤似乎是 雌激素/孕激素依赖，但尚不清楚这些卵巢如何 类固醇调节它们的生长。尽管这些肿瘤可以 生长相当迅速，它们表现出非常低的有丝分裂活动率。 肌瘤的特点是细胞外基质过多。 建议的研究集中在细胞外基质的调节上。 卵巢类固醇在子宫肌瘤和正常子宫肌层中的产生 和自分泌生长调节剂，转化生长因子-β和 甲状旁腺激素相关肽。 这项建议的具体目标是： 1.比较人子宫肌瘤和子宫肌层a)的表达。 细胞外基质蛋白I型胶原、III型胶原和 纤维连接蛋白，以及b)基质降解酶基质分解素和 胶原酶。 2.确定这些细胞外基质的表达是否 子宫肌瘤和肌层中的蛋白质和基质降解酶 受雌激素和/或黄体酮调节。 3.确定a)肌瘤是否产生更高数量的PTHrP和 2)甲状旁腺激素受体和转化生长因子-β是否调节子宫肌层的生长 胞外基质蛋白或基质降解酶的生产。 这些研究应提供有关监管的新信息。 正常子宫肌层和子宫肌层细胞外基质的产生 肌瘤。生产过剩或某些产品的降解率降低 肌瘤细胞外基质蛋白可能在很大程度上解释了其 大小的增加或“增长”。过度表达这些中的一个或多个 肌瘤的基质蛋白，增强了对 雌激素/黄体酮，或自分泌调节剂的增加 如甲状旁腺激素受体或转化生长因子-β可能是导致这一现象的一些机制 基质积聚过多。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.