Estrogen receptor a and β in uterine fibroids: a basis for altered estrogen responsiveness

Objective: To investigate the relative expression and the DNA-binding status of estrogen receptors alpha and beta in fibroids and normal myometrial tissue to explore the molecular basis of altered estrogen responsiveness of leiomyomas. Design: Biopsy samples from uterine fibroids and adjacent normal myometrial tissue at the follicular phase of the menstrual cycle. Setting: Aretaieio University Hospital and the National Hellenic Research Foundation, Athens, Greece. Patient(S): Thirty-five patients who underwent hysterectomy or myomectomy because of myoma symptoms. Intervention(S): None. Main Outcome Measure(s): Deoxyribonucleic acid-binding status of estrogen receptors alpha and beta. Result(s): The level of messenger RNA expression of estrogen receptor alpha and beta and the level of estrogen receptor as a whole are increased on average to a similar extent in leiomyomas compared with normal myometrium. Occasionally, however, estrogen receptor alpha is disproportionately increased in leiomyomas, and this appears to increase the amount of estrogen receptor alpha that binds to the estrogen-responsive element of estrogen target genes as homodimer rather than as heterodimer with estrogen receptor beta. Conclusion(s): The estrogen receptor alpha-to-estrogen receptor beta expression ratio rather than the individual expression levels determines the fraction of DNA-binding homodimers of estrogen receptor alpha and possibly the growth potential of myomas. (Fertil Steril((R)) 2008;90:1878-85. (c) 2008 by American Society for Reproductive Medicine.)