Involvement of estrogen receptor-related receptors in human ovarian endometriosis

Objective: To determine whether decreased estrogen receptor alpha (ER-α) expression in endometriotic lesions could be balanced by an increased expression of estrogen receptor-related receptors (ERRs). To evaluate whether ERR-α expression is influenced by hormonal change in fertile and menopausal women. Design: Prospective controlled study. Setting: University Hospital, Department of Gynecology. Patient(s): Twenty-five women: 20 women of reproductive age with (n = 10) and without (control; n = 10) endometriosis and 5 menopausal women. Intervention(s): Real-time polymerase chain reaction (qPCR). Immunohistochemistry. Main Outcome Measure(s): The ER and ERR expression levels were studied by reverse transcriptase-qPCR, ELISA, and immunohistochemistry using endometriotic and normal endometrial tissues. The ERR-α protein distribution was performed by immunohistochemistry in fertile and menopausal women. Result(s): Increased levels of ER-β were associated with ER-α, ERR-α, and ERR-γ reductions in ectopic tissue but not in eutopic and normal endometria. Similar levels of ERR-β were found in women with and without endometriosis. The ERR-α expression was similar in proliferative and secretory endometrial samples, whereas a down-regulation of this receptor was found in atrophic tissue. Conclusion(s): Our data confirm the up-regulation of ER-β as the principal receptor involved in the progression of human endometriosis. In addition, we found that ERR-α seems to be unresponsive to hormonal changes during the menstrual cycle.