Hum. Reprod. Advance Access originally published online on October 6, 2007
Human Reproduction 2007 22(12):3148-3158; doi:10.1093/humrep/dem310
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Estrogen metabolizing enzymes in endometrium and endometriosis
1 Research Institute GROW, University Hospital Maastricht/University Maastricht, Peter Debyelaan, The Netherlands 2 Department of Pathology, University Hospital Maastricht/University Maastricht, Peter Debyelaan, The Netherlands 3 Department of Obstetrics and Gynaecology, University Hospital Maastricht/University Maastricht, Peter Debyelaan 25 HX 6229, The Netherlands 4 Department of Gynaecology, Université de Catholique de Louvain, Brussels, Belgium 5 Solvay Pharmaceuticals Research Laboratories, Hannover, Germany
8 Correspondence address. E-mail g.dunselman{at}og.unimaas.nl
BACKGROUND: Estradiol (E2) is an important promoter of the growth of both eutopic and ectopic endometrium. The findings with regard to the expression and activity of steroidogenic enzymes in endometrium of controls, in endometrium of endometriosis patients and in endometriotic lesions are not consistent.
METHODS: In this study, we have looked at the mRNA expression and protein levels of a range of steroidogenic enzymes [aromatase, 17
-hydroxysteroid dehydrogenases (17-HSD) type 1, 2 and 4, estrogen sulfotransferase (EST) and steroid sulfatase (STS)] in eutopic and ectopic endometrium of patients (n = 14) with deep-infiltrative endometriosis as well as in disease-free endometrium (n = 48) using real-time PCR and immunocytochemistry. In addition, we evaluated their menstrual cycle-related expression patterns, and investigated their steroid responsiveness in explant cultures.
RESULTS: Aromatase and 17-HSD type 1 mRNA levels were extremely low in normal human endometrium, while mRNAs for types 2 and 4 17-HSD, EST and STS were readily detectable. Only 17-HSD type 2 and EST genes showed sensitivity to progesterone in normal endometrium. Types 1 and 2 17-HSD and STS protein was detected in normal endometrium using new polyclonal antibodies.
CONCLUSIONS: In endometriosis lesions, the balance is tilted in favor of enzymes producing E2. This is due to a suppression of types 2 and 4 17-HSD, and an increased expression of aromatase and type 1 17-HSD in ectopic endometrium.
Key words: endometriosis/steroidogenic enzymes/aromatase/estrogen metabolism/endometrium
6 Present address: Department of Molecular Diagnostics, Philips Research, High Tech Campus 11, 5656 AE Eindhoven, The Netherlands
7 Present address: Department of Pharmacology, N.V. Organon, Postbus 20, 5340 BH Oss, The Netherlands
Submitted on February 26, 2007; resubmitted on July 12, 2007; accepted on July 24, 2007.
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