Effect of RU-486 and related compounds on the proliferation of cultured macrophages.
OBJECTIVE
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.
Roberts
C P
CP
Department of Gynecology and Obstetrics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Parthasarathy
S
S
Gulati
R
R
Horowitz
I
I
Murphy
A A
AA
D000975:Antioxidants / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005938:Glucocorticoids / Q000037:antagonists & inhibitors; D006131:Growth Inhibitors / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015735:Mifepristone / Q000494:pharmacology*; D011374:Progesterone / Q000037:antagonists & inhibitors
D000975:Antioxidants; D005938:Glucocorticoids; D006131:Growth Inhibitors; D006727:Hormone Antagonists; D015735:Mifepristone; D011374:Progesterone