TRANSFORMING GROWTH-FACTOR-BETA MEDIATES THE PROGESTERONE SUPPRESSION OF AN EPITHELIAL METALLOPROTEINASE BY ADJACENT STROMA IN THE HUMAN ENDOMETRIUM
TRANSFORMING GROWTH-FACTOR-BETA MEDIATES THE PROGESTERONE SUPPRESSION OF AN EPITHELIAL METALLOPROTEINASE BY ADJACENT STROMA IN THE HUMAN ENDOMETRIUM
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DOI：
10.1073/pnas.92.16.7362
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发表时间：
1995-08-01
影响因子：
11.1
通讯作者：
OSTEEN, KG
中科院分区：
文献类型：
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作者：
BRUNER, KL;RODGERS, WH;OSTEEN, KG
与大多数正常成人组织不同，在整个生育期内，子宫内膜会发生周期性生长和组织重塑。基质金属蛋白酶 (MMP) 是一类结构相关的酶，可降解细胞外基质的特定成分，被认为是细胞外基质成分酸转换的生理相关介质。我们的实验室在循环的人类子宫内膜中鉴定出了溶基质素家族的 MMP，表明这些酶参与介导该组织中发生的广泛重塑。虽然溶基质素在增殖相关的重塑和月经相关的子宫内膜破裂期间在体内表达，但在周期的孕酮主导的分泌阶段没有基质溶素表达。我们对分离细胞类型的体外研究证实了孕酮对基质 MMP 的抑制，但发现基质衍生的旁分泌因子对于抑制上皮特异性 MMP 基质溶解素是必需的。在本报告中，我们证明转化生长因子β（TGF-β）是由子宫内膜基质响应孕酮而产生的，并且可以独立于孕酮抑制上皮基质溶解素的表达。此外，我们发现针对哺乳动物 TGF-β 亚型的抗体消除了基质-上皮共培养物中基质溶解素的黄体酮抑制，这表明 TGF-β 是人子宫内膜中基质溶解素抑制的主要介质。
Unlike most normal adult tissues, cyclic growth and tissue remodeling occur within the uterine endometrium throughout the reproductive years. The matrix metalloproteinases (MMPs), a family of structurally related enzymes that degrade specific components of the extracellular matrix are thought to be the physiologically relevant mediators of extracellular matrix composition acid turnover. Our laboratory has identified MMPs of the stromelysin family in the cycling human endometrium, implicating these enzymes in mediating the extensive remodeling that occurs in this tissue. While the stromelysins are expressed in vivo during proliferation-associated remodeling and menstruation-associated endometrial breakdown, none of the stromelysins are expressed during the progesterone-dominated secretory phase of the cycle. Our in vitro studies of isolated cell types have confirmed progesterone suppression of stromal MMPs, but a stromal-derived paracrine factor was found necessary for suppression of the epithelial-specific MMP matrilysin. In this report, we demonstrate that transforming growth factor beta (TGF-beta) is produced by endometrial stroma in response to progesterone and can suppress expression of epithelial matrilysin independent of progesterone. Additionally, we find that an antibody directed against the mammalian isoforms of TGF-beta abolishes progesterone suppression of matrilysin in stromal-epithelial cocultures, implicating TGF-beta as the principal mediator of matrilysin suppression in the human endometrium.