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.
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.


METHODS
Prospective observational study.


METHODS
Academic research center.


METHODS
Fifty patients with normal menstrual cycles who requested permanent surgical sterilization (tubal ligation) and 35 users of levonorgestrel implants.


METHODS
Endometrial biopsy.


METHODS
Expression of MMP-26, TIMP-3, and TIMP-4 by immunohistochemistry and semiquantitative analysis of staining intensity by using the H score.


RESULTS
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.


CONCLUSIONS
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.
Chegini
Nasser
N
Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida 32610, USA. cheginin@obgyn.ufl.edu
Rhoton-Vlasak
Alice
A
Williams
R Stan
RS
D000293:Adolescent; D000328:Adult; D003271:Contraceptive Agents, Female / Q000008:administration & dosage / Q000009:adverse effects*; D004343:Drug Implants; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016912:Levonorgestrel / Q000008:administration & dosage / Q000009:adverse effects*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D053505:Matrix Metalloproteinases, Secreted; D008597:Menstrual Cycle / Q000378:metabolism*; D011446:Prospective Studies; D012016:Reference Values; D013194:Staining and Labeling; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D014592:Uterine Hemorrhage / Q000139:chemically induced / Q000378:metabolism*; D000097792:Tissue Inhibitor of Metalloproteinase-4
D003271:Contraceptive Agents, Female; D004343:Drug Implants; D016912:Levonorgestrel; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4; C410599:MMP26 protein, human