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Increased Production of 17β-Estradiol in Endometriosis Lesions Is the Result of Impaired Metabolism

GROW (B.D., P.G., A.R.), School for Oncology and Developmental Biology, University Maastricht, and Department of Obstetrics and Gynecology (B.D., G.D., A.R.), University Hospital Maastricht, 6202 AZ Maastricht, The Netherlands; and Department of Obstetrics and Gynecology (T.D., C.K.), University Hospital Gasthuisberg, 3000 Leuven, Belgium

Address all correspondence and requests for reprints to: B. Delvoux. Department of Obstetrics and Gynecology, University Hospital Maastricht, P. Debyelaan 25, 6202 AZ Maastricht, The Netherlands. E-mail: b.delvoux{at}og.unimaas.nl.

Context: substantial evidence suggests that the expression of steroid metabolizing enzymes in endometriosis is altered, turning the ectopic endometrium into a source of 17β-estradiol. However, whether these differences result in a net increase in local 17β-estradiol production/activity has not been shown.

Subjects and Methods: The activities of the most important steroidogenic enzymes synthesizing and inactivating 17β-estradiol were determined by HPLC in matched eutopic and ectopic tissue from patients with endometriosis (n = 14) and in endometrium from controls (n = 20).

Results: Aromatase activity is negligible in the ectopic endometrium, whereas the activity of estrogen sulfatase is high though not different between ectopic, eutopic and control endometrium. The activity of 17β-hydroxysteroid dehydrogenases (17β-HSDs) converting estrone into 17β-estradiol is higher in the ectopic compared to the eutopic endometrium in patients. The activity of 17β-HSDs converting 17β-estradiol back to estrone is significantly lower in the ectopic compared to the eutopic endometrium of both patients and controls. To evaluate the net metabolic capacity of tissues to synthesize 17β-estradiol, we calculated the activity ratio between 17β-HSDs synthesizing versus 17β-HSDs inactivating 17β-estradiol. This ratio is significantly higher in the ectopic compared to the eutopic endometrium of patients and controls, indicating a high synthesis of 17β-estradiol in the ectopic locations. This is further supported by the elevated mRNA levels of the estrogen-responsive gene TFF1 in all ectopic compared to eutopic endometria.

Conclusion: Endometriotic lesions have higher production of 17β-estradiol than the eutopic endometrium of patients and controls. This is mostly the result of impaired metabolism.

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