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Updated: Jun 22, 2025

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Estrogen deprivation and estrogen receptor α antagonism decrease DSS colitis in female mice.

Anja Hjelt1, Santeri Anttila1, Anu Wiklund1

  • 1Institute of Biomedicine, University of Turku, Turku, Finland.

Pharmacology Research & Perspectives
|July 4, 2024
PubMed
Summary
This summary is machine-generated.

Ovarian hormones like estradiol may worsen inflammatory bowel disease (IBD). Estradiol aggravated colitis in mice, while SERM2 showed a protective effect, suggesting ERα signaling exacerbates intestinal inflammation.

Keywords:
colitisdextran sulfateestradiolestrogenestrogen receptor modulatorsinflammatory bowel diseasesreceptors

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Area of Science:

  • Gastroenterology
  • Endocrinology
  • Immunology

Background:

  • Hormonal contraception is linked to increased inflammatory bowel disease (IBD) risk in females.
  • Ovarian hormones, specifically estradiol, and estrogen receptors (ER) are implicated in intestinal inflammation progression.

Purpose of the Study:

  • To investigate the effects of estradiol and SERM2 on dextran sulfate sodium-induced colitis in mice.
  • To explore the role of estrogen receptor alpha (ERα) signaling in colitis.

Main Methods:

  • Utilized a mouse model of dextran sulfate sodium-induced colitis.
  • Compared outcomes in mice with intact ovaries versus ovariectomized (OVX) mice.
  • Administered estradiol or SERM2 prophylactically.

Main Results:

  • Ovariectomized mice showed a threefold reduced colitis score compared to intact mice.
  • Estradiol supplementation aggravated colitis in OVX mice, increasing scores to levels seen in intact mice.
  • Immune infiltration and inflammatory interleukin gene expression (Il1b, Il6, Il17a) significantly increased with estradiol supplementation in OVX mice.
  • SERM2 treatment showed a mild but consistent decrease in inflammation in intact animals.
  • Cyclooxygenase-2 induction correlated with serum estradiol levels in colitis mice.

Conclusions:

  • Estrogen receptor alpha (ERα) signaling appears to play an exacerbating role in colitis.
  • Ovarian hormone effects in colitis are significant and warrant further investigation.
  • ER antagonists may hold potential for alleviating intestinal inflammation.