Endometriosis Research Today is a free monthly online journal that collates and summarizes the latest research about Endometriosis, including details on causes, treatment, symptoms, infertility. | ||||||||
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Reduced progesterone action during endometrial maturation: a potential risk factor for the development of endometriosis.Osteen KG, Bruner-Tran KL, Eisenberg E Women's Reproductive Health Research Center, Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA. kevin.osteen@vanderbilt.edu OBJECTIVE: To discuss the role that reduced endometrial responsiveness to progesterone (P) might play in the pathophysiology of endometriosis. DESIGN: 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. Published 7 March 2005 in Fertil Steril, 83(3): 529-37.
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