A1 Refereed original research article in a scientific journal
Novel Selective Estrogen Receptor Modulator Ameliorates Murine Colitis
Authors: Polari L, Anttila S, Helenius T, Wiklund A, Linnanen T, Toivola DM, Määttä J
Publisher: MDPI
Publication year: 2019
Journal: International Journal of Molecular Sciences
Journal name in source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Journal acronym: INT J MOL SCI
Article number: ARTN 3007
Volume: 20
Issue: 12
Number of pages: 14
ISSN: 1422-0067
eISSN: 1422-0067
DOI: https://doi.org/10.3390/ijms20123007
Web address : 10.3390/ijms20123007
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/41737986
Estrogen-receptor-mediated signaling has been suggested to decrease the inflammatory response in monocyte macrophages. Previously, we showed that a novel selective estrogen receptor modulator (SERM2) promotes anti-inflammatory phenotype of monocytes in vitro. In this study, we demonstrate the potential of SERM2 in amelioration of colitis. We utilized a dextran sodium sulfate (DSS)-induced colitis model in FVB/n mice to demonstrate the effects of orally administered SERM2 on the clinical status of the mice and the histopathological changes in the colon, as well as proportion of Mrc-1 positive macrophages. SERM2 nuclear receptor affinities were measured by radioligand binding assays. Orally administered, this compound significantly alleviated DSS-induced colitis in male mice and induced local estrogen receptor activation in the inflamed colon, as well as promoting anti-inflammatory cytokine expression and infiltration of anti-inflammatory monocytes. We show that this novel drug candidate has an affinity to estrogen receptors alpha and beta and progesterone receptors, but not to glucocorticoid receptor, thus expressing unique binding properties compared to other sex steroid receptor ligands. These results indicate that novel drug candidates to alleviate inflammatory conditions of the colon could be found among sex steroid receptor activating compounds.
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