The aim of this work was to study matrix
metalloproteinase-26 (MMP-26) and tissue inhibitor
of metalloproteinases-4 (TIMP-4) in the human
endometrium. Both these enzymes may be implicated in
the implantation process. Trophoblast tissue from
human, as well as mice embryo produces pro-MMP-9.
Active MMP-9 is a proteolytic enzyme with a broad
substrate specificity. MMP-26 is an affective
activator of pro-MMP-9, and TIMP-4 is a strong
inhibitor of MMP-26.
We have shown that the endometrial expression of MMP-
26 and TIMP-4 genes is maximal in mid-cycle. The
expression pattern of both genes suggests their up-
regulation by estrogen, and down-regulation by
progesterone. This is supported by our findings of
estrogen response elements upstream the coding
sequences of both genes. Our findings suggest that
TIMP-4 is produced in the stroma only, and finally
secreted to the uterine fluid.
Results of MMP-26 and TIMP-4 expression in
hyperplastic tissue are in agreement with estrogen
mediated regulation of these genes. MMP-26 and TIMP-
4 expression in endometrial cancer decreases with
the loss of histological differentiation.