Novel Selective Estrogen Receptor Modulator Ameliorates Murine Colitis

Area of Science:

• Endocrinology
• Immunology
• Gastroenterology

Background:

• Estrogen receptor signaling may reduce inflammation in macrophages.
• A novel selective estrogen receptor modulator (SERM2) was previously shown to promote an anti-inflammatory monocyte phenotype in vitro.

Purpose of the Study:

• To investigate the potential of SERM2 in ameliorating colitis.
• To evaluate the effects of SERM2 on clinical and histopathological changes in a dextran sodium sulfate (DSS)-induced colitis model.

Main Methods:

• Utilized a DSS-induced colitis model in FVB/n mice.
• Administered SERM2 orally and assessed clinical status, colon histopathology, and Mrc-1 positive macrophage proportion.
• Measured SERM2 nuclear receptor affinities using radioligand binding assays.

Main Results:

• Orally administered SERM2 significantly alleviated DSS-induced colitis in male mice.
• SERM2 induced local estrogen receptor activation in the inflamed colon.
• Promoted anti-inflammatory cytokine expression and infiltration of anti-inflammatory monocytes.

Conclusions:

• SERM2 demonstrates therapeutic potential for inflammatory conditions like colitis.
• The novel compound exhibits unique binding properties to estrogen receptors α and β and progesterone receptors.
• Sex steroid receptor activating compounds represent a promising avenue for developing novel anti-inflammatory drugs for colon conditions.