Effect of RU-486 and related compounds on the proliferation of cultured macrophages

C P Roberts, Roberts CP, Parthasarathy S, S Parthasarathy, Rita Gulati, Gulati R, R Gulati, I Horowitz, Horowitz I, Ira Horowitz, Murphy AA, A A Murphy
American journal of reproductive immunology (New York, N.Y. : 1989) · 1995 · vol. 34(4) , pp. 248–256 · doi:10.1111/j.1600-0897.1995.tb00949.x · PMID:8579763 · W2039902350
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RU-486, progesterone, and a RU-486 analog inhibited macrophage proliferation, with RU-486 and progesterone showing synergistic effects, while RU-486 antagonized dexamethasone-stimulated growth.

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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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Condition tags

endometriosis

MeSH descriptors

Growth Inhibitors Macrophages Mifepristone Antioxidants Antioxidants Antioxidants Cell Division Cell Division Cell Division Glucocorticoids Glucocorticoids Glucocorticoids Growth Inhibitors Growth Inhibitors Hormone Antagonists Hormone Antagonists Hormone Antagonists Humans Humans Macrophages

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