Human Reproduction Update Advance Access originally published online on August 25, 2005
Human Reproduction Update 2006 12(1):49-56; doi:10.1093/humupd/dmi034
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Aromatase and other steroidogenic genes in endometriosis: translational aspects
Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
1 To whom correspondence should be addressed at: Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. E-mail: s-bulun{at}northwestern.edu
Submitted on May 26, 2005; revised on July 16, 2005; accepted on July 25, 2005
Endometriosis is a common, chronic and estrogen-dependent gynaecological disorder associated with pelvic pain and infertility. In addition to, or perhaps as a consequence of, immune, environmental and genetic factors, endometriotic lesions show high estradiol (E2) biosynthesis and low E2 inactivation compared with normal endometrium. Current medical therapies of pain, which aim to lower circulating E2 concentrations, are not effective in at least half of these patients. We and others recently demonstrated the expression of a few steroidogenic genes in endometriosis. The most important genes in this group are steroidogenic acute regulatory protein (StAR) and aromatase. Both are essential for E2 production. Prostaglandin E2 (PGE2) is the most potent known stimulator of both StAR and aromatase. PGE2 production in endometriosis is up-regulated by increased levels of the enzyme cyclo-oxygenase-2 (COX-2) in this tissue. COX-2 in turn is stimulated by E2, interleukin-1ß (IL-1ß) and PGE2 itself in endometrial and endometriotic cells. Thus, there is a positive feedback loop that favours continuous formation of E2 and PGE2 in endometriosis. These basic findings led to recent phase-II studies employing aromatase inhibitors in the treatment of endometriosis. Aromatase inhibitors treat both postmenopausal and premenopausal endometriosis at least as effectively as the existing medical treatments. In premenopausal women, we and others administered aromatase inhibitors in combination with an ovarian-suppressant treatment. In this review, we emphasize the most recent basic studies in detail and provide a short summary of recent clinical trials.
Key words: aromatase inhibitors / aromatase / cyclo-oxygenase-2 / endometriosis / steroidogenic acute regulatory protein
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Olivares, M. Bilotas, R. Buquet, M. Borghi, C. Sueldo, M. Tesone, and G. Meresman Effects of a selective cyclooxygenase-2 inhibitor on endometrial epithelial cells from patients with endometriosis Hum. Reprod., August 20, 2008; (2008) den315v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-C. Hsu, C.-W. Lu, B.-M. Huang, M.-H. Wu, and S.-J. Tsai Cyclic Adenosine 3',5'-Monophosphate Response Element-Binding Protein and CCAAT/Enhancer-Binding Protein Mediate Prostaglandin E2-Induced Steroidogenic Acute Regulatory Protein Expression in Endometriotic Stromal Cells Am. J. Pathol., August 1, 2008; 173(2): 433 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hirata, Y. Osuga, K. Hamasaki, O. Yoshino, M. Ito, A. Hasegawa, Y. Takemura, Y. Hirota, E. Nose, C. Morimoto, et al. Interleukin (IL)-17A Stimulates IL-8 Secretion, Cyclooxygensase-2 Expression, and Cell Proliferation of Endometriotic Stromal Cells Endocrinology, March 1, 2008; 149(3): 1260 - 1267. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Hudelist, K. Czerwenka, J. Keckstein, C. Haas, A. Fink-Retter, D. Gschwantler-Kaulich, E. Kubista, and C.F. Singer Expression of Aromatase and Estrogen Sulfotransferase in Eutopic and Ectopic Endometrium: Evidence for Unbalanced Estradiol Production in Endometriosis Reproductive Sciences, December 1, 2007; 14(8): 798 - 805. [Abstract] [PDF]
|
|
|
|
 |
|
 Q. Xue, Z. Lin, Y.-H. Cheng, C.-C. Huang, E. Marsh, P. Yin, M. P Milad, E. Confino, S. Reierstad, J. Innes, et al. Promoter Methylation Regulates Estrogen Receptor 2 in Human Endometrium and Endometriosis Biol Reprod, October 1, 2007; 77(4): 681 - 687. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Wieser, M. Cohen, A. Gaeddert, J. Yu, C. Burks-Wicks, S. L. Berga, and R. N. Taylor Evolution of medical treatment for endometriosis: back to the roots? Hum. Reprod. Update, September 1, 2007; 13(5): 487 - 499. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Takemura, Y. Osuga, O. Yoshino, A. Hasegawa, T. Hirata, Y. Hirota, E. Nose, C. Morimoto, M. Harada, K. Koga, et al. Metformin Suppresses Interleukin (IL)-1{beta}-Induced IL-8 Production, Aromatase Activation, and Proliferation of Endometriotic Stromal Cells J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3213 - 3218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Xue, Z. Lin, P. Yin, M. P. Milad, Y.-H. Cheng, E. Confino, S. Reierstad, and S. E. Bulun Transcriptional Activation of Steroidogenic Factor-1 by Hypomethylation of the 5' CpG Island in Endometriosis J. Clin. Endocrinol. Metab., August 1, 2007; 92(8): 3261 - 3267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Lin, O. Ercan, J. Raza, C. P. Burren, S. M. Creighton, R. J. Auchus, M. T. Dattani, and J. C. Achermann Variable Phenotypes Associated with Aromatase (CYP19) Insufficiency in Humans J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 982 - 990. [Abstract] [Full Text] [PDF]
|
|