This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Andersen, J. Articles by Miksicek, R. J. Search for Related Content PubMed PubMed Citation Articles by Andersen, J. Articles by DyReyes, V. M. Articles by Barbieri, R. L. Articles by Coachman, D. M. Articles by Miksicek, R. J. Social Bookmarking                   What's this?

Leiomyoma Primary Cultures Have Elevated Transcriptional Response to Estrogen Compared With Autologous Myometrial Cultures

Departments of Obstetrics and Gynecology and Pharmacology, State University of New York at Stony Brook, New York; Department of Obstetrics and Gynecology, Harvard Medical School, Boston, Massachusetts; Department of Obstetrics and Gynecology, School of Medicine, SUNY at Stony Brook, Stony Brook, NY 11794-8091

Victor M. DyReyes, BS

Robert L. Barbieri, MD

Denise M. Coachman, AAS

Richard J. Miksicek, PhD

Departments of Obstetrics and Gynecology and Pharmacology, State University of New York at Stony Brook, New York; Department of Obstetrics and Gynecology, Harvard Medical School, Boston, Massachusetts

Objective: We tested the hypothesis that uterine leiomyomas are hypersensitive to estrogen as compared with autologous human myometrium.

Methods: 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.

Results: Myometrial and leiomyoma primary cultures were transcriptionally responsive to the estrogen ethinly estradiol (eE₂). The partial agonist tamoxifen did not elicit a positive transcriptional response and antagonized estrogen-induced transciption 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 myometrical 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 leuteal 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.

Conclusions: 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.

Key Words: Leiomyomas • myometrium • estrogen • transcription • human

Journal of the Society for Gynecologic Investigation, Vol. 2, No. 3, 542-551 (1995)
DOI: 10.1177/107155769500200307


CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?