Skip Navigation



Mol. Hum. Reprod. Advance Access published online on October 8, 2004
Molecular Human Reproduction, doi:10.1093/molehr/gah113
© 2004 by Oxford University Press
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
10/12/853    most recent
gah113v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Oehler, M. K.
Right arrow Articles by Kieback, D. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Oehler, M. K.
Right arrow Articles by Kieback, D. G.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received June 28, 2004
Revised August 30, 2004
Accepted September 8, 2004

Article

Functional characterization of somatic point mutations of the human estrogen receptor {alpha} (hER{alpha}) in adenomyosis uteri

Martin K. Oehler 1 {dagger}, Holger Greschik 2 *, Dagmar-C. Fischer 3, Xiaowen Tong 1, Roland Schuele 4, and Dirk G. Kieback 5

1 Department of Obstetrics and Gynaecology, Baylor College of Medicine, Houston, TX, USA; Department of Obstetrics and Gynaecology, Freiburg University Medical Center, Freiburg, Germany
2 Department of Obstetrics and Gynaecology, Freiburg University Medical Center, Freiburg, Germany
3 Department of Obstetrics and Gynaecology, Freiburg University Medical Center, Freiburg, Germany; Department of Obstetrics and Gynaecology, Maastricht University Medical Center, Maastricht, The Netherlands
4 Department of Obstetrics and Gynaecology, Freiburg University Medical Center, Freiburg, Germany
5 Department of Obstetrics and Gynaecology, Baylor College of Medicine, Houston, TX, USA; Department of Obstetrics and Gynaecology, Freiburg University Medical Center, Freiburg, Germany; Department of Obstetrics and Gynaecology, Maastricht University Medical Center, Maastricht, The Netherlands


  Abstract

Endometriosis and adenomyosis uteri are chronic, benign diseases caused by the presence of endometrial tissue in ectopic locations, e.g. peritoneal or deep inside the myometrial wall of the uterus and/or in the rectovaginal septum. Although adenomyosis might be considered as a special form of endometriosis, both conditions differ with respect to clinical symptoms and treatment. Induction of a hypo-estrogenic state alone or in combination with surgical removal of the extra-uterine lesion is mostly sufficient for treatment of peritoneal endometriosis. By contrast, adenomyosis uteri rarely responds to hormonal therapy and usually requires a hysterectomy for cure. Consequently, the role of steroid hormone receptors with respect to the aetiology of either condition is still a matter of discussion. Using PCR/single strand conformation polymorphism analysis, we identified somatic estrogen receptor (ER) {alpha} gene mutations in three out of 55 samples from adenomyosis uteri. Functional characterization revealed that two of the mutant ER{alpha} proteins display severely impaired DNA-binding and transactivation properties secondary to an altered response to estrogens or changes in epidermal growth factor-mediated ligand-independent activation. Although the exact mechanism remains unknown, we suggest that mutation-related silencing of estrogen responsiveness might render endometriotic cells resistant to hypo-estrogenic conditions thereby accounting for failure of estrogen-ablative therapy in adenomyosis.

Keywords: adenomyosis uteri; endometriosis; human estrogen receptor alpha; somatic mutation; steroid receptor.

*M.K.O. and H.G. contributed equally


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.