Inhibition of steroid sulfatase decreases endometriosis in an in vivo murine model
Open accessAbstract
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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E2MATE has shown promising results in human endometrial explants and a mouse model of endometriosis.
“Another inhibitor, estradiol-3-O-sufamate (E2MATE), used on human endometrial explants and in a mouse model of endometriosis, has shown some promising results [108].”
From Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders (2018) · cites this paper as [108]
Cites
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“This supports the conclusion that production of estradiol and its subsequent circulation is not dependent on the STS enzyme pathway but, as widely recognized, on the aromatase pathway in the ovaries and fatty tissue (Simpson, 2003).”
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“Endometriosis is known to be an estrogen-dependent disorder (Rizner, 2009).”
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The Regulation of Steroid Action by Sulfation and Desulfation
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“Another inhibitor, estradiol-3-O-sufamate (E2MATE), used on human endometrial explants and in a mouse model of endometriosis, has shown some promising results [108].”
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- Authors
- Colette, S., Defrere, S., Lousse, J. C., Van Langendonckt, A., Gotteland, J. P., Loumaye, E., & Donnez, J.
- Affiliations
- Cliniques Universitaires Saint-Luc (BE)
- PregLem (Switzerland) (CH)
- Corresponding author
- Donnez, J.
- ORCID
- Donnez, J.
- Venue
- Human Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-03-25
- Volume
- 26
- Issue
- 6
- Pages
- 1362-1370
- ISSN
- 0268-1161 (ISSN-L)
- 1460-2350
- OpenAlex
- W2098841434
- Cited by
- 45
- References
- 7
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 5 · 2017: 2 · 2016: 3 · 2015: 5 · 2014: 3 · 2013: 4 · 2012: 7
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- Locations
- Human Reproduction (publishedVersion)
- PubMed (publishedVersion)
- Digital Access to Libraries (submittedVersion, other-oa)
- Funders
- Fonds De La Recherche Scientifique - FNRS
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- endometriosis, steroid sulfatase, estrogen synthesis, endometrial explants, progesterone receptor, plasma estradiol, endometriotic lesions, stromal edema, mouse model
- MeSH terms
- Animals, Cells, Cultured, Endometriosis, Estradiol, Female, Humans, Uterus, Steryl-Sulfatase, Mice
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