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Circulating ovarian steroids and endometrial matrix metalloproteinases (MMPs)
Patrick Henriet1, Patricia B Cornet, Pascale Lemoine
1Cell Biology Unit, Christian de Duve Institute of Cellular Pathology, Université Catholique de Louvain, Brussels, Belgium.
Abstract:
Recent studies strongly suggest that matrix metalloproteinases (MMPs) play a key role in the initiation of menstrual bleeding in the human endometrium upon the fall of ovarian steroid serum concentrations by inducing the degradation of the extracellular matrix of this mucosa. MMPs are also involved in abnormal endometrial bleeding and have been identified in endometriotic foci. In all cases, they are associated with areas of extracellular matrix breakdown. This paper reviews the literature on the regulation by estradiol and progesterone of the expression and activation of MMPs, and of the expression of their tissue inhibitors (TIMPs), (i) in the endometrium in situ during normal cycle, (ii) during artificial cycles in spayed monkeys, and (iii) in cultures of endometrial explants or purified cells. Whereas progesterone consistently decreases the activity of endometrial MMPs, its effects vary in intensity, duration, and pattern between MMPs as well as among experimental systems. The contribution and limitations of the various investigations are therefore discussed. The focal heterogeneity points to additional local controls of the expression and activation of MMPs in human endometrium, acting beyond the general inhibitory role of progesterone, for example, by cytokines. Focal changes in type or abundance of sex steroid receptors also could be responsible for spatial variation in the expression of MMPs in the endometrium and endometriotic lesions.
Insights
Matrix metalloproteinases (MMPs) initiate menstrual bleeding by degrading the extracellular matrix in the human endometrium. Progesterone generally reduces MMP activity, but local factors also influence MMPs in endometrial and endometriotic tissues.
Area of Science:
- Reproductive biology
- Endocrinology
- Gynecology
Background:
- Matrix metalloproteinases (MMPs) are implicated in extracellular matrix degradation during menstruation and in abnormal endometrial bleeding.
- MMPs are present in endometriotic tissues, associated with matrix breakdown.
Purpose of the Study:
- To review the regulation of MMPs and their inhibitors (TIMPs) by estradiol and progesterone in the human endometrium.
- To analyze MMP regulation during normal and artificial menstrual cycles and in endometrial cell cultures.
Main Methods:
- Literature review of studies on endometrial MMPs and TIMPs.
- Analysis of data from in situ endometrium, artificial cycles in monkeys, and endometrial cell cultures.
- Discussion of the limitations and contributions of various experimental systems.
Main Results:
- Progesterone consistently inhibits endometrial MMP activity, though effects vary in intensity and pattern.
- Focal heterogeneity in MMP expression suggests local regulatory controls beyond progesterone, such as cytokines.
- Variations in sex steroid receptor expression may explain spatial differences in MMPs within the endometrium and endometriosis.
Conclusions:
- MMPs are key players in endometrial extracellular matrix breakdown and menstrual bleeding initiation.
- While progesterone inhibits MMPs, local factors and sex steroid receptor expression significantly modulate MMP activity in the endometrium and endometriotic lesions.
- Further research is needed to understand the complex local regulation of MMPs in gynecological tissues.