Matrix metalloproteinase expression in Macaca mulatta endometrium: Evidence for zone-specific regulatory tissue gradients

Matrix metalloproteinases (MMPs) are highly expressed in the human endometr ium during menstruation, and these enzymes participate in the cyclic destru ction and regeneration characteristic of the primate endometrium. To examin e hormonal regulation of MMPs in vivo, we evaluated MMP expression and loca lization in the endometrium of ovariectomized rhesus macaques under various hormonal conditions. Although all MMPs were up-regulated by progesterone ( P-4) withdrawal, their expression declined spontaneously after menstruation in the absence of P-4. Of 7 MMPs examined, only matrilysin and stromelysin -3 were suppressed any further when P-4 levels were experimentally re-eleva ted. MMP expression was confined to the upper functionalis zone during mens truation, but after menstrual breakdown was complete, matrilysin and the ti ssue inhibitor of MMPs, TIMP-1, shifted expression from the functionalis to the basalis zone in the absence of both estradiol and P-4. The spiral arte ries in the functionalis, but not the basalis, were intense foci of MMP and TIMP-1 expression. Menstruation and MMP expression after P-4 withdrawal we re similar in both the presence and absence of estradiol. In sum, endometri al MMPs in vivo are strongly up-regulated by P-4 withdrawal, but zone-speci fic tissue gradients greatly influence the pattern and degree of MMP expres sion.