Osteen Kevin G, Bruner-Tran Kaylon L, Eisenberg Esther
Women's Reproductive Health Research Center, Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Fertil Steril. 2005 Mar;83(3):529-37. doi: 10.1016/j.fertnstert.2004.11.026.
To discuss the role that reduced endometrial responsiveness to progesterone (P) might play in the pathophysiology of endometriosis.
A review of experimental evidence regarding the failure of P to regulate the expression of matrix metalloproteinases (MMPs) in the endometrium of patients with endometriosis.
CONCLUSION(S): Progesterone and locally produced differentiation factors act cooperatively to reduce MMP expression by maternal endometrial cells within the pro-inflammatory micro-environment of early pregnancy. Our in vitro studies with normal human endometrium demonstrate that prior P exposure not only down-regulates MMP expression, but also limits the ability of locally produced proinflammatory cytokines to stimulate expression of these enzymes. In contrast, endometrial tissues from women with endometriosis demonstrate an altered response to P, allowing a continuous expression of MMPs throughout the secretory phase. Although the factors that influence the loss of P sensitivity in the endometrium of patients with endometriosis have not yet been defined, alterations in cell-cell communication seem to contribute to dysregulated MMP expression. Specifically, proinflammatory cytokines produced by epithelial cells oppose stromal cell responses to P, inhibiting production of key differentiation factors necessary for cell-specific MMP regulation. The resulting loss in normal MMP regulation enhances the invasive capacity of endometrial tissue, promoting ectopic establishment in an experimental model.
探讨子宫内膜对孕酮（P）反应性降低在子宫内膜异位症病理生理学中可能发挥的作用。
综述关于孕酮无法调节子宫内膜异位症患者子宫内膜中基质金属蛋白酶（MMPs）表达的实验证据。
孕酮和局部产生的分化因子协同作用，以降低妊娠早期促炎微环境中母体子宫内膜细胞的MMP表达。我们对正常人子宫内膜的体外研究表明，预先暴露于孕酮不仅会下调MMP表达，还会限制局部产生的促炎细胞因子刺激这些酶表达的能力。相比之下，子宫内膜异位症患者的子宫内膜组织对孕酮的反应发生改变，使得MMP在整个分泌期持续表达。虽然尚未明确影响子宫内膜异位症患者子宫内膜对孕酮敏感性丧失的因素，但细胞间通讯的改变似乎导致了MMP表达失调。具体而言，上皮细胞产生的促炎细胞因子对抗基质细胞对孕酮的反应，抑制细胞特异性MMP调节所需关键分化因子的产生。正常MMP调节的丧失增强了子宫内膜组织的侵袭能力，在实验模型中促进异位着床。
