Skip to main content
Top
Published in: Archives of Gynecology and Obstetrics 4/2011

01-10-2011 | General Gynecology

Endometrial expression of estrogen receptor β and its splice variants in patients with and without endometriosis

Authors: Ingolf Juhasz-Böss, Claudia Fischer, Claus Lattrich, Maciej Skrzypczak, Eduard Malik, Olaf Ortmann, Oliver Treeck

Published in: Archives of Gynecology and Obstetrics | Issue 4/2011

Login to get access

Abstract

Background

The 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.

Methods

Total 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).

Results

ERα, 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.

Conclusions

ERα, 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.
Literature
1.
go back to reference Sampson J (1927) Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the pelvic cavity. Am J Obstet Gynecol 14:422–469 Sampson J (1927) Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the pelvic cavity. Am J Obstet Gynecol 14:422–469
2.
go back to reference Lecce 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):1379–1386PubMedCrossRef Lecce 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):1379–1386PubMedCrossRef
3.
go back to reference Matsuzaki 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):559–564PubMedCrossRef Matsuzaki 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):559–564PubMedCrossRef
4.
go back to reference Jazaeri 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):6965–6969PubMedCrossRef Jazaeri 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):6965–6969PubMedCrossRef
5.
go back to reference Fujimoto 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):133–140PubMedCrossRef Fujimoto 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):133–140PubMedCrossRef
6.
go back to reference Skrzypczak 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):783–787PubMedCrossRef Skrzypczak 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):783–787PubMedCrossRef
7.
go back to reference Chakravarty 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):905–913PubMedCrossRef Chakravarty 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):905–913PubMedCrossRef
8.
go back to reference Brandenberger 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):651–655PubMedCrossRef Brandenberger 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):651–655PubMedCrossRef
9.
go back to reference Fujimoto J, Hirose R, Sakaguchi H, Tamaya T (1999) Expression of oestrogen receptor-alpha and -beta in ovarian endometriomata. Mol Hum Reprod 5(8):742–747PubMedCrossRef Fujimoto J, Hirose R, Sakaguchi H, Tamaya T (1999) Expression of oestrogen receptor-alpha and -beta in ovarian endometriomata. Mol Hum Reprod 5(8):742–747PubMedCrossRef
10.
go back to reference Matsuzaki 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):1198–1205PubMedCrossRef Matsuzaki 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):1198–1205PubMedCrossRef
11.
go back to reference Hudelist 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):1249–1256PubMedCrossRef Hudelist 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):1249–1256PubMedCrossRef
12.
go back to reference Xue 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):681–687PubMedCrossRef Xue 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):681–687PubMedCrossRef
13.
go back to reference Wang 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):1650–1656PubMedCrossRef Wang 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):1650–1656PubMedCrossRef
14.
go back to reference Trukhacheva 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):615–622PubMedCrossRef Trukhacheva 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):615–622PubMedCrossRef
15.
go back to reference Treeck 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 Treeck 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
16.
go back to reference Treeck 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):421–433PubMedCrossRef Treeck 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):421–433PubMedCrossRef
17.
go back to reference Mylonas 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):1679–1686PubMed Mylonas 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):1679–1686PubMed
18.
go back to reference Marshburn 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 633–624PubMedCrossRef Marshburn 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 633–624PubMedCrossRef
19.
go back to reference Matsuzaki 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):753–759PubMedCrossRef Matsuzaki 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):753–759PubMedCrossRef
20.
go back to reference Cowley SM, Hoare S, Mosselman S, Parker MG (1997) Estrogen receptors alpha and beta form heterodimers on DNA. J Biol Chem 272(32):19858–19862PubMedCrossRef Cowley SM, Hoare S, Mosselman S, Parker MG (1997) Estrogen receptors alpha and beta form heterodimers on DNA. J Biol Chem 272(32):19858–19862PubMedCrossRef
21.
go back to reference Giguere V, Tremblay A, Tremblay GB (1998) Estrogen receptor beta: re-evaluation of estrogen and antiestrogen signaling. Steroids 63(5–6):335–339PubMedCrossRef Giguere V, Tremblay A, Tremblay GB (1998) Estrogen receptor beta: re-evaluation of estrogen and antiestrogen signaling. Steroids 63(5–6):335–339PubMedCrossRef
22.
go back to reference Fujimoto 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):269–277PubMedCrossRef Fujimoto 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):269–277PubMedCrossRef
Metadata
Title
Endometrial expression of estrogen receptor β and its splice variants in patients with and without endometriosis
Authors
Ingolf Juhasz-Böss
Claudia Fischer
Claus Lattrich
Maciej Skrzypczak
Eduard Malik
Olaf Ortmann
Oliver Treeck
Publication date
01-10-2011
Publisher
Springer-Verlag
Published in
Archives of Gynecology and Obstetrics / Issue 4/2011
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-010-1768-7

Other articles of this Issue 4/2011

Archives of Gynecology and Obstetrics 4/2011 Go to the issue