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Hum. Reprod. Advance Access published online on December 2, 2007
Human Reproduction, doi:10.1093/humrep/dem308
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© The Author 2007. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Inhibition of steroid sulphatase activity in endometriotic implants by 667 COUMATE: a potential new therapy

A. Purohit1, L. Fusi2, J. Brosens2, L.W.L. Woo3, B.V.L. Potter3 and M.J. Reed1,4

1 Endocrinology and Metabolic Medicine and Sterix Ltd, Imperial College London, St. Mary's Hospital, London W2 1NY, UK 2 Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London W12 ONN, UK 3 Medicinal Chemistry, Department of Pharmacy and Pharmacology and Sterix Ltd, University of Bath, Bath BA2 7AY, UK

4 Correspondence address. Tel: +44-207-886-1738; Fax: +44-207-886-1790; E-mail: m.reed{at}imperial.ac.uk

BACKGROUND: Local biosynthesis of estrogens is thought to be important for the maintenance and growth of endometriotic implants. In addition to the formation of estrogen via the aromatase pathway, steroid sulphatase (STS), which is responsible for the hydrolysis of estrogen sulphates, may be an important source of estrogens in endometriosis.

METHODS: Eutopic and ectopic endometrial samples from 14 women with minimal or mild (MM) endometriosis and from 13 women with moderate to severe (MS) endometriosis were analysed for aromatase and STS activities.

RESULTS: Aromatase and STS activity were detected in all samples. STS enzyme activity in both eutopic and ectopic endometrium was considerably higher and less variable than aromatase activity. Moreover, STS, but not aromatase, activity in endometriotic implants correlated with the severity of the disease (mean ± SEM: 203 ± 38 nmol/4 h/g wet weight tissue in MM disease versus 423 ± 44 nmol/4 h/g wet weight tissue in MS endometriosis, P < 0.001). The STS inhibitor 667 COUMATE almost completely blocked STS activity (>99%) in both eutopic and ectopic tissues.

CONCLUSIONS: The high levels of STS activity detected in ectopic endometrium and the correlation with severity of disease suggest that STS inhibitors could be useful for the treatment of endometriosis.

Key words: steroid sulphatase/aromatase/estrogen/endometriosis/therapy

Submitted on June 18, 2007; resubmitted on August 21, 2007; accepted on August 29, 2007.


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