Local activation of TGF-β1 at endometriosis sites

OBJECTIVE: To investigate the factors related to activation of transforming growth factor-beta 1 (TGF-β1) at sites of endometriosis. STUDY DESIGN: TGF-β1 is activated by plasmin, which is formed when plasminogen is activated by urokinase-type plasminogen activator (uPA). We studied these factors by immunohistochemistry or immunoassay. RESULTS: TGF-β1 protein was localized mainly in the cytoplasm of glandular epithelial cells in both endometriotic cysts and normal endometrium, but strongly positive immunostaining was significantly more common in cysts. The levels of TGF-β1, uPA and plasmin/α2-plasmin inhibitor complex were all higher in cyst fluid than in peritoneal fluid. There was little uPA protein expression in the glandular epithelium of normal endometrium, but it was prominent in the cytoplasm of glandular epithelial cells from endometriotic cysts, and strongly positive immunostaining was significantly more common in cysts. CONCLUSION: These results suggest that TGF-β1 activity is increased at sites of endometriosis due to enhanced production of both uPA and TGF-β1 by glandular epithelium and because plasmin activates TGF-β1 after being converted from plasminogen by uPA.