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 i n modulation of local immunity. Monocyte chemotactic protein-1 (MCP-I) is a chemotactic and activating factor for monocytes and is produced by multiple tumors and has antitumor effects. We investigated the expr ession of MCP-I in leiomyoma and myometrium as well as the regulatory role of steroid hormones and cytokines on MCP-1 expression and the eff ect of MCP-1 on the proliferation of leiomyoma cells. Design: Prospect ive study. Setting: University medical center. Patient(s): Women with (n = 20) or without (n = Il) leiomyoma. Intervention(s): 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. Main Outcome Measure(s): The MCP-1 mRN A was evaluated by Northern analysis. Immunoreactive MCP-I in cell cul tures was quantified by ELISA. Leiomyoma cell proliferation was assess ed with [H-3]thymidine incorporation. Result(s): The MCP-1 mRNA levels in myometrial samples were 4.7-fold higher than in the leiomyoma samp les. Myometrial MCP-1 mRNA levels were 2.4-fold higher in secretory th an in proliferative phase samples. The highest MCP-1 levels were obser ved in samples from women using GnRH analogues. Estradiol and progesti ns, alone or in combination, resulted in a decrease in MCP-1 protein p roduction. There was an increase in the proliferation of leiomyoma cel ls treated with anti-MCP-l neutralizing antibody. Conclusion(s): These findings suggest that MCP-I may have antineoplastic activity in leiom yomata and that sex steroids may be exerting their growth stimulatory effect in leiomyomata through down-regulation of MCP-1. (C)1998 by Ame rican Society for Reproductive Medicine.