Inhibition of steroid sulfatase decreases endometriosis in an in vivo murine model

S Colette, Sylvie Defrère, S Defrère, J C Lousse, Anne Van Langendonckt, A Van Langendonckt, Jean‐Pierre Gotteland, J P Gotteland, Ernest Loumaye, E Loumaye, J Donnez, Jacques Donnez
Human Reproduction · 2011 · vol. 26(6) , pp. 1362–1370 · doi:10.1093/humrep/der079 · PMID:21441545 · W2098841434
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

An STS inhibitor, E2MATE, reduced endometriosis lesion weight and size in mice by inhibiting STS activity in the uterus, liver, leukocytes, and lesions without altering systemic estradiol levels.

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The study investigated whether steroid sulfatase (STS), an enzyme involved in estrogen biosynthesis and expressed in eutopic and ectopic endometrium, plays a causal role in endometriosis development. Using an in vivo murine model, the authors inhibited STS and assessed the resulting impact on endometriosis lesions. STS inhibition decreased endometriosis in the model, supporting a role for STS in disease development. This paper is centrally about endometriosis — it tests STS inhibition as a driver of reduced endometriosis in vivo in mice.

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Abstract

BACKGROUND: Steroid sulfatase (STS) is involved in estrogen biosynthesis and expressed in eutopic and ectopic endometrium of disease-free and endometriosis patients. The present study was designed to investigate its role in endometriosis development. METHODS: Human endometrial explants were cultured on inserts for 24 h to assess the effectiveness of an STS inhibitor (STS-I), estradiol-3-O-sulfamate (E2MATE), on STS activity in endometrial tissue. Endometriosis was induced in mice, and E2MATE (or vehicle alone) was given orally for 21 days. Plasma estradiol levels were measured, and STS activity was assessed in murine organs (uterus, liver and leukocytes) and in lesions. Lesion number, weight and size (morphometry) were quantified. Lesion STS and progesterone receptor (PR) expression, proliferation and apoptosis rates were determined by immunohistochemistry. RESULTS: In vitro, addition of 1 µM E2MATE to the culture medium resulted in decreased STS activity in endometrial explants (P < 0.001). Treatment of mice with E2MATE (1.0 and 0.5 mg/kg) did not modify plasma estradiol levels, but inhibited STS activity in murine uterus (P < 0.05), liver (P < 0.001) and leukocytes (P < 0.001), as well as in induced lesions (P < 0.05). E2MATE reduced lesion weight (P < 0.01) and size (P < 0.05), but had no impact on proliferation or apoptosis rates, nor STS protein expression. Stromal edema was observed in the uterus of animals treated with E2MATE, but not in the stroma of lesions. Increased PR expression was detected in endometriotic lesions (P < 0.001). CONCLUSIONS: E2MATE was shown to effectively inhibit STS activity in endometrial tissue in vitro. In vivo, E2MATE decreased endometriosis development without affecting systemic estradiol levels. Use of STS-I could therefore be of potential interest in endometriosis treatment.
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Inhibition of steroid sulfatase decreases endometriosis in an in vivo murine model. (2011) Human Reproduction — Vol. 26, n° 6, p. 1362-1370 (2011) (2011) Human Reproduction — Vol. 26, n° 6, p. 1362-1370 (2011) Open Access - Adobe PDF - 554.17 KB - Authors - Author Colette, Sébastien UCLouvain - Author Defrere, Sylvie UCLouvain - Author Lousse, Jean-Christophe UCLouvain - Author Van Langendonckt, Anne UCLouvain - Author Donnez, Jacques UCLouvain - Abstract - Steroid sulfatase (STS) is involved in estrogen biosynthesis and expressed in eutopic and ectopic endometrium of disease-free and endometriosis patients. The present study was designed to investigate its role in endometriosis development. - Affiliations - APA - Chicago - FWB Colette, S., Defrere, S., Lousse, J.-C., Van Langendonckt, A., Gotteland, J. P., Loumaye, E., & Donnez, J. (2011). Inhibition of steroid sulfatase decreases endometriosis in an in vivo murine model. Human Reproduction, 26(6), 1362-1370. https://doi.org/10.1093/humrep/der079 (Original work published 2011)

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Endometriosis Estradiol Steryl-Sulfatase Animals Cells, Cultured Endometriosis Endometriosis Estradiol Estradiol Female Humans Mice Steryl-Sulfatase Uterus Uterus

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