Matrix metalloproteinases (MMP) are strongly implicated in menstruatio
n, Messenger RNA for proMMP-1 and -3 was detectable in normal cycle en
dometrium only peri-menstrually and menstrually, although mRNA for the
ir tissue inhibitors, TIMP-1 and TIMP-2, was present throughout the cy
cle, MMP-1, -3 and -9 were demonstrated immunohistochemically to be sp
ecifically associated with degraded tissue in menstrual endometrium, A
ctivated mast cells and eosinophils, which release regulators of MMP e
xpression and activators of latent enzymes, were also a marked feature
of menstrual endometrium. Cultured endometrial stromal cells released
MMP-1, -2, -3 and -9 and TIMP-1 and -2, whereas production by epithel
ial cells was minimal, Progesterone withdrawal from stromal cell cultu
res (for the final 4 days of a 10 day culture) increased the release o
f all four enzymes: all but MMP-2 were also stimulated by interleukin-
1 or tumour necrosis factor alpha added to short-term stromal cultures
, We postulate that an alteration in the balance of MMP and their inhi
bitors and the activation of MMP are prerequisites for tissue degradat
ion at menstruation, and that this is regulated by a combination of pr
ogesterone withdrawal and paracrine factors from epithelial and stroma
l cells and from mast cells and eosinophils.