{"paper_id":"91e69f95-bb39-4bab-82ae-9609b96fd598","body_text":"Abstract\nBackground\nThe role of estrogen receptor beta (ERβ) in pathogenesis of endometriosis remains to be elucidated. In this study, we have examined the expression of the four main ERβ transcript isoforms in human endometrial tissue in women with or without endometriosis.\nMethods\nTotal RNA was isolated from native endometrial tissue and transcript levels of ERα, β1, β2, β4, β5 were analyzed by means of RT-PCR. We compared the results with regard to menstrual cycle phase as well as to presence or absence of endometriosis. We prospectively harvested the endometrium of ten women without endometriosis (five for each cycle phase) and eight patients with endometriosis (five in the proliferative phase, three in the secretory phase).\nResults\nERα, β1, β2, and β5 transcripts were detected in both cycle phases. During the proliferative phase, healthy women had a significantly higher ERα/ERβ1-ratio than patients with endometriosis. Irrespective of the cycle phase, ERα-mRNA level was significantly higher than transcript levels of ERβ isoforms.\nConclusions\nERα, β1, β2, and β5 are expressed in human endometrium. The individual receptors differed in terms of expression strength but there was no relevant change during the cycle. The decreased ERα/ERβ1-ratio in proliferative endometrium of endometriosis patients suggest that ERβ1 might be involved in the pathogenesis of endometriosis. Further studies should be undertaken to substantiate the role of ERβ in endometrial pathology.\nSimilar content being viewed by others\nReferences\nSampson J (1927) Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the pelvic cavity. Am J Obstet Gynecol 14:422–469\nLecce G, Meduri G, Ancelin M, Bergeron C, Perrot-Applanat M (2001) Presence of estrogen receptor beta in the human endometrium through the cycle: expression in glandular, stromal, and vascular cells. J Clin Endocrinol Metab 86(3):1379–1386\nMatsuzaki S, Fukaya T, Suzuki T, Murakami T, Sasano H, Yajima A (1999) Oestrogen receptor alpha and beta mrna expression in human endometrium throughout the menstrual cycle. Mol Hum Reprod 5(6):559–564\nJazaeri AA, Nunes KJ, Dalton MS, Xu M, Shupnik MA, Rice LW (2001) Well-differentiated endometrial adenocarcinomas and poorly differentiated mixed mullerian tumors have altered er and pr isoform expression. Oncogene 20(47):6965–6969\nFujimoto J, Sun WS, Misao R, Sakaguchi H, Aoki I, Toyoki H, Tamaya T (2003) Expression of estrogen receptor beta exon-deleted variant mrnas in ovary and uterine endometrium. J Steroid Biochem Mol Biol 84(2–3):133–140\nSkrzypczak M, Bieche I, Szymczak S, Tozlu S, Lewandowski S, Girault I, Radwanska K, Szczylik C, Jakowicki JA, Lidereau R, Kaczmarek L (2004) Evaluation of mrna expression of estrogen receptor beta and its isoforms in human normal and neoplastic endometrium. Int J Cancer 110(6):783–787\nChakravarty D, Srinivasan R, Ghosh S, Gopalan S, Rajwanshi A, Majumdar S (2007) Estrogen receptor beta1 and the beta2/betacx isoforms in nonneoplastic endometrium and in endometrioid carcinoma. Int J Gynecol Cancer 17(4):905–913\nBrandenberger AW, Lebovic DI, Tee MK, Ryan IP, Tseng JF, Jaffe RB, Taylor RN (1999) Oestrogen receptor (er)-alpha and er-beta isoforms in normal endometrial and endometriosis-derived stromal cells. Mol Hum Reprod 5(7):651–655\nFujimoto J, Hirose R, Sakaguchi H, Tamaya T (1999) Expression of oestrogen receptor-alpha and -beta in ovarian endometriomata. Mol Hum Reprod 5(8):742–747\nMatsuzaki S, Murakami T, Uehara S, Canis M, Sasano H, Okamura K (2001) Expression of estrogen receptor alpha and beta in peritoneal and ovarian endometriosis. Fertil Steril 75(6):1198–1205\nHudelist G, Keckstein J, Czerwenka K, Lass H, Walter I, Auer M, Wieser F, Wenzl R, Kubista E, Singer CF (2005) Estrogen receptor beta and matrix metalloproteinase 1 are coexpressed in uterine endometrium and endometriotic lesions of patients with endometriosis. Fertil Steril 84(Suppl 2):1249–1256\nXue Q, Lin Z, Cheng YH, Huang CC, Marsh E, Yin P, Milad MP, Confino E, Reierstad S, Innes J, Bulun SE (2007) Promoter methylation regulates estrogen receptor 2 in human endometrium and endometriosis. Biol Reprod 77(4):681–687\nWang Z, Yoshida S, Negoro K, Kennedy S, Barlow D, Maruo T (2004) Polymorphisms in the estrogen receptor beta gene but not estrogen receptor alpha gene affect the risk of developing endometriosis in a japanese population. Fertil Steril 81(6):1650–1656\nTrukhacheva E, Lin Z, Reierstad S, Cheng YH, Milad M, Bulun SE (2009) Estrogen receptor (er) beta regulates eralpha expression in stromal cells derived from ovarian endometriosis. J Clin Endocrinol Metab 94(2):615–622\nTreeck O, Juhasz-Boess I, Lattrich C, Horn F, Goerse R, Ortmann O (2007) Effects of exon-deleted estrogen receptor beta transcript variants on growth, apoptosis and gene expression of human breast cancer cell lines. Breast Cancer Res Treat\nTreeck O, Pfeiler G, Mitter D, Lattrich C, Piendl G, Ortmann O (2007) Estrogen receptor {beta}1 exerts antitumoral effects on sk-ov-3 ovarian cancer cells. J Endocrinol 193(3):421–433\nMylonas I, Jeschke U, Shabani N, Kuhn C, Kriegel S, Kupka MS, Friese K (2005) Normal and malignant human endometrium express immunohistochemically estrogen receptor alpha (er-alpha), estrogen receptor beta (er-beta) and progesterone receptor (pr). Anticancer Res 25(3A):1679–1686\nMarshburn PB, Zhang J, Bahrani-Mostafavi Z, Mostafavi BZ, Marroum MC, Mougeot JL, Roshon MJ (2004) Estrogen receptor-alpha messenger rna variants that lack exon 5 or exon 7 are coexpressed with wild-type form in human endometrium during all phases of the menstrual cycle. Am J Obstet Gynecol 191(2):626–633 discussion 633–624\nMatsuzaki S, Uehara S, Murakami T, Fujiwara J, Funato T, Okamura K (2000) Quantitative analysis of estrogen receptor alpha and beta messenger ribonucleic acid levels in normal endometrium and ovarian endometriotic cysts using a real-time reverse transcription-polymerase chain reaction assay. Fertil Steril 74(4):753–759\nCowley SM, Hoare S, Mosselman S, Parker MG (1997) Estrogen receptors alpha and beta form heterodimers on DNA. J Biol Chem 272(32):19858–19862\nGiguere V, Tremblay A, Tremblay GB (1998) Estrogen receptor beta: re-evaluation of estrogen and antiestrogen signaling. Steroids 63(5–6):335–339\nFujimoto J, Sakaguchi H, Aoki I, Toyoki H, Tamaya T (2002) Clinical implications of the expression of estrogen receptor-alpha and -beta in primary and metastatic lesions of uterine endometrial cancers. Oncology 62(3):269–277\nConflict of interest\nThe author(s) indicated no potential conflicts of interest.\nAuthor information\nAuthors and Affiliations\nCorresponding author\nRights and permissions\nAbout this article\nCite this article\nJuhasz-Böss, I., Fischer, C., Lattrich, C. et al. Endometrial expression of estrogen receptor β and its splice variants in patients with and without endometriosis. Arch Gynecol Obstet 284, 885–891 (2011). https://doi.org/10.1007/s00404-010-1768-7\nReceived:\nAccepted:\nPublished:\nIssue date:\nDOI: https://doi.org/10.1007/s00404-010-1768-7","source_license":"CC0","license_restricted":false}