TRANSFORMING GROWTH-FACTOR-BETA MEDIATES THE PROGESTERONE SUPPRESSIONOF AN EPITHELIAL METALLOPROTEINASE BY ADJACENT STROMA IN THE HUMAN ENDOMETRIUM

Unlike most normal adult tissues, cyclic growth and tissue remodeling occur within the uterine endometrium throughout the reproductive years . The matrix metalloproteinases (MMPs), a family of structurally relat ed enzymes that degrade specific components of the extracellular matri x are thought to be the physiologically relevant mediators of extracel lular matrix composition acid turnover. Our laboratory has identified MMPs of the stromelysin family in the cycling human endometrium, impli cating these enzymes in mediating the extensive remodeling that occurs in this tissue. While the stromelysins are expressed in vivo during p roliferation-associated remodeling and menstruation-associated endomet rial breakdown, none of the stromelysins are expressed during the prog esterone-dominated secretory phase of the cycle. Our in vitro studies of isolated cell types have confirmed progesterone suppression of stro mal MMPs, but a stromal-derived paracrine factor was found necessary f or suppression of the epithelial-specific MMP matrilysin. In this repo rt, we demonstrate that transforming growth factor beta (TGF-beta) is produced by endometrial stroma in response to progesterone and can sup press expression of epithelial matrilysin independent of progesterone. Additionally, we find that an antibody directed against the mammalian isoforms of TGF-beta abolishes progesterone suppression of matrilysin in stromal-epithelial cocultures, implicating TGF-beta as the princip al mediator of matrilysin suppression in the human endometrium.