Leiomyoma primary cultures have elevated transcriptional response to estrogen compared with autologous myometrial cultures

Abstract

We tested the hypothesis that uterine leiomyomas are hypersensitive to estrogen as compared with autologous human myometrium. The estrogen-induced transcriptional responses of uterine leiomyoma and myometrial primary cultures were determined by transient expression assays. The relative levels of estrogen receptor (ER) in myometrial and leiomyoma tissues were determined by immunoblot. Myometrial and leiomyoma primary cultures were transcriptionally responsive to the estrogen ethinyl estradiol (eE2). The partial agonist tamoxifen did not elicit a positive transcriptional response and antagonized estrogen-induced transcription in the cultured cells. The responses of hormone-treated leiomyoma cells averaged 4.5-fold higher than those in controls with no hormone (P = .0001). The myometrial cells from women in the follicular phase exhibited little if any transcriptional response to eE2, whereas myometrial cells from women in the luteal phase had a transcriptional response to eE2 averaging threefold higher than that in no-hormone controls (P = .0083). Differences in response between autologous myometrial and leiomyoma cultures were statistically significant by the two-tailed Wilcoxon paired nonparametric signed-rank test (n = 11; P = .0137). These differences were more pronounced in cultures from women in the follicular or early luteal phase. In addition, the levels of ER increased in follicular and early luteal phase myometrial tissues, which correlated well with the number of days from the last menstrual period (n = 8; r = 0.9046; P = .002). Estrogen-receptor levels in myometrial tissues decreased during the late luteal phase. Levels in leiomyoma tissues did not follow the same pattern as in the myometrium and were elevated in tissues taken from women in the follicular phase. Autologous leiomyoma cultures have a significantly higher response to estrogen than do matched myometrial cultures, especially if the cultures are derived from the follicular phase. The levels of ER in leiomyoma tissue from women in the follicular phase are significantly elevated.