RU486-induced growth inhibition of human endometrial cells

Objective: To determine the direct action of RU486 on endometrial cell prol iferation and to differentiate whether thr antioxidant or the antiprogester one property of RU486 is predominately responsible for its effect on cell g rowth. Design: In vitro study comparing the effects of RU486 (antiprogesterone and antioxidant), reduced RU486 (antioxidant), ZK112,993 (antiprogesterone), a nd lazaroid U74,500A (antioxidant) on endometrial cell growth. The human en dometrial cell line EM42 was used in transient transfection assays to confi rm the relative antiprogesterone potency of the various compounds. Setting: Academic medical center. Patient(s): Women presenting with pelvic pain or infertility and diagnosed with endometriosis at time of surgery or women desiring tubal ligation with a normal pelvis (controls). Intervention(s): Endometrial cell cultures were treated with RU486, reduced RU486, lazaroid U74,500A, and ZK112,993. Main Outcome Measure(s): Tritiated thymidine incorporation was used to asse ss cell growth. Inhibition of progesterone induction of transiently transfe cted reporter plasmids was used to measure antiprogesterone activity of com pounds studied. Result(s): RU486 reduced cell growth in a dose-dependent fashion of the end ometrial cell lines EM42 and RL95-2 and of endometrial and endometriosis ce lls from primary culture. After being reduced, RU486 lost most of its antip rogesterone activity but retained its antiproliferative properties. ZK112,9 93 was similar in potency to RU486 as a progesterone antagonist but did not significantly modify endometrial cell growth. Lazaroid U74,500A was devoid of antiprogesterone activity but was shown to be a potent antiproliferativ e agent. Conclusion(s): RU486 has a direct inhibitory effect on human endometrial ce ll growth. This activity appears to be at least partly mediated through its antioxidant property. (C)2000 by American Society for Reproductive Medicin e.