Uterine leiomyomas express myometrial contractile-associated proteins involved in pregnancy-related hormone signaling

Objective: We used an animal model to study uterine leiomyoma in the context of pregnancy-associated changes in gene expression and to determine how they might modulate tumor growth. Methods: Spontaneous tumors and normal myometrium were collected from Eker rats and compared with myometrial samples from pregnant animals. A leiomyoma-derived cell line was also used to assess pregnancy-related changes in gene expression and to determine the impact of signaling by the oxytocin receptor. Results: Eker rat leiomyomas expressed several pregnancy-related genes, including connexin 43, oxytocin receptor (OTR), and cyclooxygenase (COX)-1; however, the tumors did not express COX-2, which is expressed in the parturient myometrium. The leiomyoma-derived cell lines also expressed OTR, which responds to estrogen, binds to oxytocin, and exhibits a calcium flux when stimulated with oxytocin. The OTR signaling mediated by oxytocin inhibited estrogen-stimulated growth of leiomyoma cells. Conclusions: Leiomyoma cells expressed many genes of the parturient myometrium, including OTRs, but were deficient in COX-2 expression. Signaling via the OTR appears to inhibit estrogen-induced cell proliferation, suggesting that signaling by this receptor might help mediate the protective effect of pregnancy on this disease.