Regulation of monocyte chemotactic protein-1 expression in human endometrial stromal cells by estrogen and progesterone

There is a cyclicity in the number of endometrial macrophages that is most likely secondary to changes in steroid hormone levels. One cytokine that controls macrophage migration is monocyte chemotactic protein-1 (MCP-1). In the endometrium, highest levels of MCP-1 are detected perimenstrually, when estrogen levels are low; however, when estrogen levels are high (around the time of ovulation), MCP-1 levels are lowest. We hypothesized that sex steroids may be involved in the regulation of macrophage migration by regulating MCP-1 expression. We investigated the regulation of MCP-1 expression in human endometrial stromal cells by estradiol 17 beta (E-2) and progestins. We found that MCP-1 mRNA levels decreased in response to E-2 (5 x 10(-8) M), with biphasic nadirs at 8 h and 24 h. MCP-1 protein production was also inhibited by E-2 in a concentration-dependent manner. Tamoxifen, an anti-estrogen, alone (10(-7) M) did not affect MCP-1 expression, but it reversed the E-2-induced inhibition up to 80%. Progesterone (10-7 M) alone slightly decreased MCP-1 levels, and the combination of E-2 and progesterone further decreased them, but that decrease was not different from that observed using E-2 treatment alone. In summary, we found that E-2 inhibits MCP-1 expression in endometrial stromal cells, and we speculate that E-2 may control endometrial macrophage migration by regulating MCP-1 expression.