Expression of matrix metalloproteinase-26 and tissue inhibitor of matrix metalloproteinase-3 and -4 in endometrium throughout the normal menstrual cycle and alteration in users of levonorgestrel implants who experience irregular uterine bleeding

Nasser Chegini, Alice Rhoton-Vlasak, R. Stanley Williams, R Stan Williams
Fertility and sterility · 2003 · vol. 80(3) , pp. 564–570 · doi:10.1016/s0015-0282(03)00797-0 · PMID:12969699 · W1974150229
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This study investigated the expression of matrix metalloproteinase-26 and its inhibitors, TIMP-3 and TIMP-4, in the endometrium during the normal menstrual cycle and in levonorgestrel implant users with irregular bleeding.

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Abstract

OBJECTIVE: To determine the expression of matrix metalloproteinase (MMP-26) and tissue inhibitor of MMP (TIMP) in the endometrium of women with normal menstrual cycles compared with users of levonorgestrel implants. DESIGN: Prospective observational study. SETTING: Academic research center. PATIENT(S): Fifty patients with normal menstrual cycles who requested permanent surgical sterilization (tubal ligation) and 35 users of levonorgestrel implants. INTERVENTION(S): Endometrial biopsy. MAIN OUTCOME MEASURE(S): Expression of MMP-26, TIMP-3, and TIMP-4 by immunohistochemistry and semiquantitative analysis of staining intensity by using the H score. RESULT(S): Endometrium from women with a normal menstrual cycle and users of levonorgestrel implants expresses MMP-26, TIMP-3, and TIMP-4. These substances are present in various types of endometrial cells; expression is strongest in surface and glandular epithelial cells, followed by vascular endothelial and endometrial stromal cells. Inflammatory and immune-related cells also stained strongly for MMP-26 and TIMPs. Semiquantitative analysis of the staining intensity of endometrial epithelial and stromal cells indicated that expression of MMP-26, TIMP-3, and TIMP-4 peaks during the early to mid-luteal phase. Expression of MMP-26 is elevated in users of levonorgestrel implants who experienced irregular uterine bleeding. CONCLUSION(S): Endometrial expression of MMP-26 and TIMP-4 is present throughout the menstrual cycle and is elevated during the early to mid-luteal phase in normally cycling women. Further elevations in MMP-26 are seen in users of levonorgestrel implants who experience irregular uterine bleeding. These substances thus seem to play a role in hormonal regulation and endometrial tissue remodeling.

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MeSH descriptors

Contraceptive Agents, Female Endometrium Levonorgestrel Matrix Metalloproteinases Menstrual Cycle Tissue Inhibitor of Metalloproteinase-3 Tissue Inhibitor of Metalloproteinases Uterine Hemorrhage Adolescent Adult Contraceptive Agents, Female Contraceptive Agents, Female Drug Implants Endometrium Female Humans Immunohistochemistry Immunohistochemistry Levonorgestrel Levonorgestrel

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