Effect of gonadotropin-releasing hormone agonists on monocyte chemotactic protein-1 production and macrophage infiltration in leiomyomatous uterus.

Abstract Objective: The level of monocyte chemotactic protein-1 (MCP-1), a potent chemoattractant for monocytes, is fivefold higher in myometrium than in leiomyoma. We have previously shown that myometrium from women using GnRH agonists (GnRH-a) express the highest levels of MCP-1, which has antiproliferative effects on leiomyoma cells. We hypothesized that MCP-1 may have a direct paracrine effect in leiomyomatous uterus rather than acting by way of chemoattraction of macrophages. Design: Cross-sectional study. Setting: University medical center. Patient(s): Women with leiomyoma (n = 32). Intervention(s): Immunohistochemical analysis performed in the myometrium and leiomyoma of women receiving (n = 11) and not receiving (n = 21) GnRH-a treatment. Main Outcome Measure(s): The MCP-1 levels and macrophage counts determined by immunohistochemistry in the myometrium and leiomyoma of women receiving GnRH-a were compared to the levels and counts in women not receiving GnRH-a. Result(s): Samples from all 11 patients using GnRH-a revealed strong MCP-1 staining, whereas staining was only weakly present in 11 and absent in 10 samples from patients not receiving GnRH-a, revealing a significant difference in MCP-1 expression between GnRH-a users versus nonusers ( P =.006). The number of tissue macrophages between GnRH-a users and nonusers was not significantly different. Conclusion(s): We found that there is an increase in the MCP-1 protein expression in the myometrium of women receiving GnRH-a treatment. On the other hand, we have not observed a difference in the macrophage count and distribution with GnRH-a treatment, suggesting a potentially direct antiproliferative role for MCP-1 rather than acting by means of chemoattraction of macrophages.