Effect of RU-486 and Related Compounds on the Proliferation of Cultured Macrophages

Authors


Department of Gynecology and Obstetrics, P.O. Box 21246, Emory University School of Medicine, Atlanta, GA 30322.

Abstract

PROBLEM: Macrophages are implicated in the pathophysiology of endometriosis and are influenced by anti-inflammatory steroids as well as anti-oxidants.

METHODS: We tested the effect of RU-486, an antiprogesterone, antiglucocorticoid and an antioxidant, on the proliferation of RAW macrophages.

RESULTS: The incorporation of 3H-thymidine was significantly inhibited by both progesterone and RU-486. Progesterone and RU-486, in combination, synergistically inhibited macrophage growth. In contrast, dexamethasone-stimulated growth was antagonized by RU-486 in a dose dependent manner. ZK 112,993 which is structurally related to RU-486 but lacks antioxidant properties, also inhibited thymidine incorporation. The synergistic effect of RU-486 and ZK 112,993 with progesterone implicate a mechanism of action separate from receptor bound antagonists. A cell permeable antioxidant, pyrrolidine dithiocarbamate was very effective in inhibiting the incorporation of 3H-thymidine into cells.

CONCLUSIONS: These results suggest novel therapeutic modalities in the management of endometriosis via antiglucocorticoid as well as antioxidant mechanisms.

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