Transforming growth factor-β3 is expressed at high levels in leiomyoma where it stimulates fibronectin expression and cell proliferation

Objective: To investigate the expression of TGF-beta 3 in leiomyoma and myometrium as well as the effect of TGF-beta 3 on the expression of fibronectin and on the proliferation of leiomyoma and myometrial cells. Design: Observational and in vitro experimental study. Setting: University medical center. Patient(s): Women with (n = 18) leiomyoma. Intervention(s): First TGF-beta 3 mRNA and protein levels in myometrium and leiomyoma were measured, and then myometrial and leiomyoma cells in culture were treated with TGF-beta 3. Main Outcome Measure(s): TGF-beta 3 and fibronectin mRNA were evaluated by Northern analysis. Myometrial and leiomyoma cell proliferation was assessed with use of [H-3]thymidine incorporation. Result(s): The TGF-beta 3 mRWA level in the leiomyoma samples was 3.5-fold higher than in the myometrial samples. The highest TGF-beta 3 mRNA level was observed in leiomyoma samples from midsecretory phase and was 5-fold higher than in proliferative phase samples. Fibronectin mRNA expression also was higher in the leiomyoma than in the myometrium. TGF-beta 3 induced fibronectin expression in leiomyoma cells and directly stimulated myometrial and leiomyoma cell proliferation in cultures. Conclusion(s): These findings suggest that TGF-beta 3 may be mediating the growth-promoting effects of sex steroids on leiomyomas by playing a role in the fibrogenic process and cell proliferation that characterize these tumors. (Fertil Steril(R) 2000;13:1006-11. (C) 2000 by American Society for Reproductive Medicine).