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

Fertil Steril. 2003 Sep;80(3):564-70. doi: 10.1016/s0015-0282(03)00797-0.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Contraceptive Agents, Female / administration & dosage
  • Contraceptive Agents, Female / adverse effects*
  • Drug Implants
  • Endometrium / metabolism*
  • Female
  • Humans
  • Immunohistochemistry / methods
  • Levonorgestrel / administration & dosage
  • Levonorgestrel / adverse effects*
  • Matrix Metalloproteinases / metabolism*
  • Matrix Metalloproteinases, Secreted
  • Menstrual Cycle / metabolism*
  • Prospective Studies
  • Reference Values
  • Staining and Labeling
  • Tissue Inhibitor of Metalloproteinase-3 / metabolism*
  • Tissue Inhibitor of Metalloproteinase-4
  • Tissue Inhibitor of Metalloproteinases / metabolism*
  • Uterine Hemorrhage / chemically induced
  • Uterine Hemorrhage / metabolism*

Substances

  • Contraceptive Agents, Female
  • Drug Implants
  • Tissue Inhibitor of Metalloproteinase-3
  • Tissue Inhibitor of Metalloproteinases
  • Levonorgestrel
  • MMP26 protein, human
  • Matrix Metalloproteinases
  • Matrix Metalloproteinases, Secreted