Pregnancy, parturition, and prostaglandins: Defining uterine leiomyomas

Leiomyomas, benign smooth muscle tumors of the uterus, are the most common gynecologic neoplasm in women. Studies with surgically resected human tissu es and primary cultures have revealed that several genes are differentially expressed in leiomyomas compared to matched normal myometrium. An estrogen -driven pattern of gene expression in leiomyomas, similar to that seen in n ormal myometrium during pregnancy and parturition, is associated with a per sistent inappropriate response of neoplastic myometrial smooth muscle cells to ovarian hormones. This is possibly due to aberrant expression levels or signaling via estrogen and progesterone receptors. We propose the hypothes is that uterine leiomyomas mimic a differentiated myometrial cell at pregna ncy and exhibit a hypersensitivity to sex steroid hormones that prevents th e cells from responding to normal apoptotic or dedifferentiation signals an d from returning to a nongravid phenotype. Support of this hypothesis is de rived from experimental studies in female Eker rats that develop uterine le iomyomas with many similarities to the human disease. Our hypothesis accoun ts for the benign nature of these tumors and their high incidence in women during the reproductive years. By identifying the factors that participate in parturition and involution of the pregnant myometrium, we may better def ine uterine leiomyomas and thus identify novel targets for therapeutic stra tegies to treat these tumors.