MATRIX METALLOPROTEINASES IN NORMAL MENSTRUATION

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.