Involvement of estrogen receptor-related receptors in human ovarian endometriosis
ABSTRACT 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.
Prospective controlled study.
University Hospital, Department of Gynecology.
Twenty-five women: 20 women of reproductive age with (n = 10) and without (control; n = 10) endometriosis and 5 menopausal women.
Real-time polymerase chain reaction (qPCR). Immunohistochemistry.
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.
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.
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.
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ABSTRACT: Endometriosis is a complex and challenging disease that involves aberrant adhesion, growth, and progression of endometrial tissues outside of the uterine cavity, and there is evidence to suggest that estrogen plays a key role in its development and progression. Numerous in vivo clinical studies have described the ectopic expression and regulation of estrogen receptor (ER) and progesterone receptor (PR) in the different types of endometriosis compared to normal or eutopic endometrium. However, we have noticed that conflicting and contradictory results have been presented in terms of ER subtype (ERα and ERβ) and PR isoform (PRA and PRB) expression. Both ER and PR are transcription factors and ER/PR-mediated responses depend on the coordinated, opposing, and compensatory functions of ER subtypes and PR isoforms. Moreover, analysis of the uterine phenotypes of ERα/ERβ and PRA/PRB knockout mice indicates that different ER subtypes and PR isoforms mediate distinct responses to steroid hormones and play different roles in uterine function. In this review, we outline studies that have elucidated the molecules and signaling pathways that are linked to ER and/or PR signaling pathways in the development and progression of endometriosis.American Journal of Translational Research 01/2014; 6(2):104-113. · 3.23 Impact Factor
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ABSTRACT: Endometriosis is an estrogen-dependent gynecological disease where endometrium-like tissue grows outside uterine cavity. Endometriotic cell proliferation is stimulated by estrogens acting predominantly via their nuclear receptors. Estrogen receptors (ESR1, ESR2) are ligand activated transcription factors whose activation is dependent on the cell-specific dynamic expression of the receptors, on the interacting proteins and on the ligand availability. The different types of endometriotic lesions, peritoneal, deep, and ovarian endometriosis, may respond to estrogens differentially due to differences in the expression of the receptors and interacting proteins, and due to potential differences in the ligand availability regulated by the local estrogen synthesis. This review summarizes the current knowledge of estrogen synthesizing enzymes and estrogen receptors in different types of endometriosis lesions. Further studies are still needed to define the possible differences in steroid metabolism in different types of endometriotic lesions.Molecular and Cellular Endocrinology 08/2011; 358(2):146-54. DOI:10.1016/j.mce.2011.08.022 · 4.24 Impact Factor
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ABSTRACT: Introduction: Endometriosis, histologically defined as the presence of endometrium-like tissue - glands and stroma - that develops outside of the uterine cavity, is still an enigmatic disease responsible for pelvic pain and infertility. The current treatments of endometriosis are surgery and hormonal therapies that act by suppressing ovulation and/or directly on steroid receptors located in endometriotic lesions. Areas covered: New hormonal and non-hormonal therapies are being developed for the treatment of endometriosis-related pain. The authors review the state of advancement and the results of novel treatments studied in registered trials ( www.ClinicalTrials.gov ). Cellular signaling pathways activated in endometriotic cells, which constitute potential targets for future treatments, are also described. Expert opinion: Therapeutic research efforts should focus on identifying and testing substances capable of acting locally on the lesions themselves, without interfering with ovulation, in order to be efficacious on both pain symptoms and infertility.Expert Opinion on Emerging Drugs 03/2012; DOI:10.1517/14728214.2012.668885 · 3.28 Impact Factor