Epidermal growth factor and transforming growth factor-β serve opposite roles in the regulation of stromelysin-1 versus prolactin secretion by human endometrial stromal cells

The cyclic expression of matrix metalloproteinases of the stromelysin family in the human endometrium implicates these enzymes in mediating tissue remodeling in this organ. We have determined that regulation of the expression of an epithelial-specific stromelysin is under the interactive control of an ovarian steroid and the local production of transforming growth factor-beta by endometrial stroma. Specialized stromal cells of the endometrium are appreciated as the most steroid sensitive cell type within this tissue but also respond to the action of growth factors, including epidermal growth factor (EGF) and transforming growth factor-beta (TGF-beta). While the action of EGF is often associated with the effects of estradiol on endometrial,growth, the action of TGF-beta appears to act in concert with the differentiation-promoting action of progesterone. In this study, we examined the potential interactive role(s) of EGF and TGF-beta in the endometrial stroma in association with the growth-related secretion of stromelysin-1 versus the differentiation-related secretion of prolactin. For these studies, we established an organ culture system that maintains normal in vivo-like cell-cell communication as well as st system which allows stromal cell decidualization in vitro. Utilizing organ cultures of tissue obtained during the proliferative menstrual interval, we found that either progesterone or TGF-beta treatment alone suppressed stromelysin-1 secretion while estradiol or EGF treatment maintained secretion of this proliferation associated enzyme. Studies of isolated stromal cells revealed that progesterone treatment promoted acquisition of a differentiated cellular phenotype and secretion of the differentiation marker protein, prolactin. Similar cultures treated with EGF maintained a fibroblastic appearance and released negligible amounts of prolactin while cultures treated with TGF-beta secreted elevated levels of prolactin. These results demonstrate that EGF and TGF-beta have opposite effects on stromal cell secretion of the growth-related protein, stromerysin-1, compared to the secretion of the differentiation-related protein, prolactin.