Absence of aromatase protein and mRNA expression in endometriosis.

[en] BACKGROUND: Aromatase has been reported to be involved in estrogen biosynthesis and expressed in eutopic and ectopic endometrium of endometriosis patients. The objective of the present study was to investigate its expression and localization in three distinct types of endometriosis. METHODS: Human peritoneal, ovarian and rectovaginal endometriotic lesions and matched eutopic endometrium were collected from patients during laparoscopy. Aromatase protein localization (immunohistochemistry, n = 63) and mRNA expression [quantitative polymerase chain reaction (Q-PCR), n = 64] were assessed. RESULTS: No aromatase protein was detected by immunohistochemistry in either the glandular or stromal compartment of endometriotic lesions or eutopic endometrium, while it was strong in placental syncytiotrophoblasts, granulosa and internal theca cells from pre-ovulatory follicles, and luteal cells from corpus luteum. By Q-PCR, low but discernible levels of aromatase expression were found in endometriomas, probably due to follicular expression. Transcripts for aromatase were barely detectable in only a few peritoneal and rectovaginal endometriotic lesions, and a few eutopic endometrium samples, probably due to contaminating surrounding tissues (adipose tissue, intact peritoneum). CONCLUSIONS: Unlike previous studies, we observed no aromatase protein in any of the endometriosis types, and barely detectable aromatase mRNA expression, suggesting that locally produced aromatase (within endometriotic lesions) may be less implicated in endometriosis development than previously postulated. Potential factors responsible for these discrepancies are discussed.

Disciplines :

Reproductive medicine (gynecology, andrology, obstetrics)
Anatomy (cytology, histology, embryology...) & physiology

Author, co-author :

Colette, S.

Lousse, J. C.

Defrère, S.

Curaba, M.

Heilier, J. F.

Van Langendonckt, A.

Mestdagt, Mélanie ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement

Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique - Labo de biologie des tumeurs et du développement

Loumaye, E.

Donnez, J.

Language :

English

Title :

Absence of aromatase protein and mRNA expression in endometriosis.

Publication date :

2009

Journal title :

Human Reproduction

ISSN :

0268-1161

eISSN :

1460-2350

Publisher :

Oxford University Press, Oxford, United Kingdom

Volume :

Issue :

Pages :

2133-41

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 07 February 2010

Statistics

Number of views

130 (5 by ULiège)

Number of downloads

115 (0 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

Bibliography

Acien P, Velasco I, Gutierrez M, Martinez-Beltran M. Aromatase expression in endometriotic tissues and its relationship to clinical and analytical findings. Fertil Steril 2007;88:32-38.
Aghajanova L, Hamilton A, Kwintkiewicz J, Vo KC, Giudice LC. Steroidogenic enzyme and key decidualization marker dysregulation in endometrial stromal cells from women with versus without endometriosis. Biol Reprod 2009;80:105-114.
Attar E, Tokunaga H, Imir G, Bertan Yilmaz M, Redwine D, Putman M, Gurates B, Attar R, Yaegashi N, Hales DB et al. Prostaglandin E2 via steroidogenic factor-1 coordinately regulates transcription of steroidogenic genes necessary for estrogen synthesis in endometriosis. J Clin Endocrin Metab 2008;. in press.
Brosens J, Verhoeven H, Campo R, Gianaroli L, Gordts S, Hazekamp J, Hagglund L, Mardesic T, Varila E, Zech J et al. High endometrial aromatase P450 mRNA expression is associated with poor IVF outcome. Hum Reprod 2004;19:352-356.
Bukulmez O, Hardy DB, Carr BR, Word RA, Mendelson CR. Inflammatory status influences aromatase and steroid receptor expression in endometriosis. Endocrinology 2007;149:1190-1204.
Bulun SE, Yang S, Fang Z, Gurates B, Tamura M, Zhou J, Sebastian S. Role of aromatase in endometrial disease. J Steroid Biochem Mol Bio 2001;79:19-25.
Bulun SE, Lin Z, Imir G, Amin S, Demura M, Yilmaz B, Martin R, Utsunomiya H, Thung S, Gurates B et al. Regulation of aromatase expression in estrogen-responsive breast and uterine disease: from bench to treatment. Pharmacol Rev 2005;57:359-383.
Conley A, Hinshelwood M. Mammalian aromatases. Reproduction 2001;121:685-695.
Dassen H, Punyadeera C, Kamps R, Delvoux B, Van Langendonckt A, Donnez J, Husen B, Thole H, Dunselman G, Groothuis P. Estrogen-metabolizing enzymes in endometrium and endometriosis. Hum Reprod 2007;22:3148-3158.
Delvoux B, Groothuis P, D'Hooghe T, Kyama C, Dunselman G, Romano A. Increased production of 17beta-estradiol in endometriosis lesions is the result of impaired metabolism. J Clin Endocrinol Metab 2008;. in press.
Dheenadayalu K, Mak I, Gordts S, Campo R, Higham J, Puttemans P, White J, Christian M, Fusi L, Brosens J. Aromatase P450 messenger RNA expression in eutopic endometrium is not a specific marker for pelvic endometriosis. Fertil Steril 2002;78:825-829.
Donnez J, Van Langendonckt A, Casanas-Roux F, Van Gossum JP, Pirard C, Jadoul P, Squifflet J, Smets M. Current thinking on the pathogenesis of endometriosis. Gynecol Obstet Invest 2002;54:52-62.
Fabian CJ. The what, why and how of aromatase inhibitors: hormonal agents for treatment and prevention of breast cancer. Int J Clin Pract 2007;61:2051-2063.
Fazleabas AT, Brudney A, Chai D, Langoi D, Bulun SE. Steroid receptor and aromatase expression in baboon endometriotic lesions. Fertil Steril 2003;80:820-827.
Fechner S, Husen B, Thole H, Schmidt M, Gashaw I, Kimmig R, Winterhager E, Grümmer R. Expression and regulation of estrogen-converting enzymes in ectopic human endometrial tissue. Fertil Steril 2007;88:1029-1038.
Heilier JF, Donnez J, Defrère S, Van Kerckhove V, Donnez O, Lison D. Serum dioxin-like compounds and aromatase (CYP19) expression in endometriotic tissues. Toxicol Lett 2006a;167:238-244.
Heilier JF, Donnez O, Van Kerckhove V, Lison D, Donnez J. Expression of aromatase (P450 aromatase/CYP19) in peritoneal and ovarian endometriotic tissues and deep endometriotic (adenomyotic) nodules of the rectovaginal septum. Fertil Steril 2006b;85:1516-1518.
Hudelist G, Czerwenka K, Keckstein J, Haas C, Fink-Retter A, Gschwantler-Kaulich D, Kubista E, Singer CF. Expression of aromatase and estrogen sulfotransferase in eutopic and ectopic endometrium: evidence for unbalanced estradiol production in endometriosis. Reprod Sci 2007;14:798-805.
Ishihara H, Kitawaki J, Kado N, Koshiba H, Fushiki S, Honjo H. Gonadotropin-releasing hormone agonist and danazol normalize aromatase cytochrome P450 expression in eutopic endometrium from women with endometriosis, adenomyosis, or leiomyomas. Fertil Steril 2003;79:735-742.
Kitawaki J, Noguchi T, Amatsu T, Maeda K, Tsukamoto K, Yamamoto T, Fushiki S, Osawa Y, Honjo H. Expression of aromatase cytochrome P450 protein and messenger ribonucleic acid in human endometriotic and adenomyotic tissues but not in normal endometrium. Biol Reprod 1997;57:514-519.
Kitawaki J,Kusuki I, KoshibaH, Tsukamoto K, Fushiki S,Honjo H.Detection of aromatase cytochrome P-450 in endometrial biopsy specimens as a diagnostic test for endometriosis. Fertil Steril 1999a;72:1100-1106.
Kitawaki J, Kusuki I, Koshiba H, Tsukamoto K, Honjo H. Expression of aromatase cytochrome P450 in eutopic endometrium and its application as a diagnostic test for endometriosis. Gynecol Obstet Invest 1999b;48:21-28.
Kyama CM, Overbergh L, Mihalyi A, Meuleman C, Mwenda JM, Mathieu C, D'Hooghe TM. Endometrial and peritoneal expression of aromatase, cytokines, and adhesion factors in women with endometriosis. Fertil Steril 2007;89:301-310.
Matsuzaki S, CanisM, Pouly JL, Déchelotte PJ, Mage G. Analysis of aromatase and 17β-hydroxysteroid dehydrogenase type 2messenger ribonucleic acid expression in deep endometriosis and eutopic endometrium using laser capture microdissection. Fertil Steril 2006;85:308-313.
Mihalyi A, Simsa P, Mutinda KC, Meuleman C, Mwenda JM, D'Hooghe TM. Emerging drugs in endometriosis. Expert Opin Emerg Drugs 2006;11:503-524.
Murakami K, Nomura K, Shinohara K, Kasai T, Shozu M, Inoue M. Danazol inhibits aromatase activity of endometriosis-derived stromal cells by a competitive mechanism. Fertil Steril 2006;86:291-297.
Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril 1997;68:585-596.
Noble LS, Simpson ER, Johns A, Bulun SE. Aromatase expression in endometriosis. J Clin Endocrinol Metab 1996;81:174-179.
Noble LS, Takayama K, Zeitoun KM, Putman JM, Johns DA, Hinshelwood MM, Agarwal VR, Zhao Y, Carr BR, Bulun SE. Prostaglandin E2 stimulates aromatase expression in endometriosis-derived stromal cells. J Clin Endocrinol Metab 1997;82:600-606.
Patwardhan S, Nawathe A, Yates D, Harrison GR, Khan KS. Systematic review of the effects of aromatase inhibitors on pain associated with endometriosis. BJOG 2008;115:818-822.
Perls M. Nachweis von Eisenoxyd in gewissen Pigmenten. Virchows Arch 1867;39:42-48.
Purohit A, Fusi L, Brosens J,Woo LWL, Potter BVL, Reed MJ. Inhibition of steroid sulphatase activity in endometriotic implants by 667 COUMATE: a potential new therapy. Hum Reprod 2007;23:290-297.
Sampson JA. Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 1927;14:422-469.
Sasano H, Okamoto M, Mason JI, Simpson ER, Mendelson CR, Sasano N, Silverberg SG. Immunolocalization of aromatase, 17α-hydroxylase and side-chain-cleavage cyochromes P-450 in the human ovary. J Reprod Fertil 1989;85:163-169.
Simpson ER, Mahendroo MS, Means AD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD et al. Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 1994;15:342-355.
Simpson ER, Clyne C, Speed C, Rubin G, Bulun S. Tissue-specific estrogen biosynthesis and metabolism. Ann N Y Acad Sci 2001;949:58-67.
Smuc T, Ribic Pucelj M, Sinkovec J, Husen B, Thole H, Nanisnik Rizner T. Expression analysis of the genes involved in estradiol and progesterone action in human ovarian endometriosis. Gynecol Endocrinol 2007;23:105- 111.
Smuc T, Hevir N, Ribic?-Pucelj M, Husen B, Thole H, Riz?ner TL. Disturbed estrogen and progesterone action in ovarian endometriosis. Mol Cell Endocrinol 2008;. in press.
Turner KJ, Macpherson S, Millar MR, McNeilly AS, Williams K, Cranfield M, Groome NP, Sharpe RM, Fraser HM, Saunders PTK. Development and validation of a new monoclonal antibody to mammalian aromatase. J Endocrinol 2002;172:21-30.
Velasco I, Rueda J, Acien P. Aromatase expression in endometriotic tissues and cell cultures of patients with endometriosis. Mol Hum Reprod 2006;12:377-381.
Wölfler MM, Nagele F, Kolbus A, Seidl S, Schneider B, Huber JC, Tschgguel W. A predictive model for endometriosis. Hum Reprod 2005;20:1702-1708.