Expression and hormonal regulation of monocyte chemotactic protein-1 in myometrium and leiomyomata.
OBJECTIVE
The pathogenesis of leiomyoma likely involves interactions of sex steroids with paracrine growth factors or cytokines resulting in modulation of local immunity. Monocyte chemotactic protein-1 (MCP-1) is a chemotactic and activating factor for monocytes and is produced by multiple tumors and has antitumor effects. We investigated the expression of MCP-I in leiomyoma and myometrium as well as the regulatory role of steroid hormones and cytokines on MCP-1 expression and the effect of MCP-1 on the proliferation of leiomyoma cells.


METHODS
Prospective study.


METHODS
University medical center.


METHODS
Women with (n = 20) or without (n = 11) leiomyoma.


METHODS
First. MCP-1 messenger RNA (mRNA) levels in myometrium and leiomyoma were measured, and then myometrial and leiomyoma cells in culture were treated with steroid hormones and cytokines.


METHODS
The MCP-1 mRNA was evaluated by Northern analysis. Immunoreactive MCP-1 in cell cultures was quantified by ELISA. Leiomyoma cell proliferation was assessed with [3H]thymidine incorporation.


RESULTS
The MCP-1 mRNA levels in myometrial samples were 4.7-fold higher than in the leiomyoma samples. Myometrial MCP-1 mRNA levels were 2.4-fold higher in secretory than in proliferative phase samples. The highest MCP-1 levels were observed in samples from women using GnRH analogues. Estradiol and progestins, alone or in combination, resulted in a decrease in MCP-1 protein production. There was an increase in the proliferation of leiomyoma cells treated with anti-MCP-1 neutralizing antibody.


CONCLUSIONS
These findings suggest that MCP-1 may have antineoplastic activity in leiomyomata and that sex steroids may be exerting their growth stimulatory effect in leiomyomata through down-regulation of MCP-1.
Sozen
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Department of Obstetrics and Gynecology, Yale University School of Medicine, New Haven, Connecticut 06520-8063, USA.
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D000328:Adult; D000368:Aged; D002455:Cell Division / Q000187:drug effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004338:Drug Combinations; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018231:Leiomyomatosis / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D009215:Myometrium / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018932:Chemokine CCL2; D016207:Cytokines; D004338:Drug Combinations; D012333:RNA, Messenger; D011374:Progesterone; D004958:Estradiol