The matrix metalloproteinase (MMP) system is composed of the enzymatic component, the MMPs, and the enzyme inhibitory component, the tissue inhibitors of metalloproteinases or TIMPs. It is well established that the MMP system plays a critical role during the normal development and growth of the endometrium as well as many other physiological processes. Because of the necessity for the balance between MMP and TIMP, it is not surprising that aberrant expression of MMPs and TIMPs is associated with the pathophysiology of many diseases. Included in this list is the female disease endometriosis, a disease in which endometrial tissue grows outside of the uterus usually within the pelvic cavity. Both endometriotic (ectopic) endometrial tissue as well as the eutopic endometrium from women with the disease exhibit altered patterns of MMP and TIMP expression which favor tissue invasion/remodeling by the endometriotic tissue. As such, it has been proposed that successful modulation of the MMP system to limit or prevent the invasive events necessary for endometriosis development and/or progression may open new avenues to the medical management of endometriosis. This review will present general knowledge of the MMP system relative to the pathophysiology of the endometriosis as well as address its potential value in relation to the treatment of the disease.
Tissue inhibitors of metalloproteinases (TIMPs) are expressed within the uteri of virtually all species where they are postulated to control extracellular matrix turnover, cellular apoptosis, and proliferation. The objective of the current study was to examine the steroidal regulation of uterine TIMP expression and to determine the potential role of the TIMP-1 gene product in this regulation. To accomplish these goals, ovariectomized female TIMP-1 wild-type and null mice were treated with estradiol, progesterone, or estradiol and progesterone and killed at various times after steroid administration. Estradiol induced a significant reduction in uterine TIMP-3 expression in wild-type mice at 8 and 24 h post-steroid administration, but the ability of this steroid to decrease TIMP-3 expression was impaired in the uteri of TIMP-1 null mice. Further, estrogen-induced uterine wet-weight gain/edema was enhanced in the TIMP-1 null mice, and the antiestrogen compound ICI 182780 or progesterone could only partially block this estrogenic effect. It is concluded from this study that steroidal modulation of uterine TIMP-3 expression and regulation of wet-weight gain/edema are altered in TIMP-1 null mice. These observations suggest that steroids induce uterine TIMP-1 expression and, in turn, that TIMP-1 influences TIMP-3 mRNA expression and uterine edema.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.