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


METHODS
Cross-sectional study.


METHODS
University medical center.


METHODS
Women with leiomyoma (n = 32).


METHODS
Immunohistochemical analysis performed in the myometrium and leiomyoma of women receiving (n = 11) and not receiving (n = 21) GnRH-a treatment.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Sozen
I
I
Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.
Senturk
L M
LM
Arici
A
A
D002452:Cell Count; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D003430:Cross-Sectional Studies; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D006801:Humans; D018231:Leiomyomatosis / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000473:pathology*; D009215:Myometrium / Q000378:metabolism* / Q000473:pathology; D014594:Uterine Neoplasms / Q000378:metabolism* / Q000473:pathology
D018932:Chemokine CCL2; D007987:Gonadotropin-Releasing Hormone