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However, in preclinical models of estradiol in colitis, results have been inconsistent, and both alleviating and aggravating effects have been reported. Previously, we suggested that the estrogen receptor \u03b1 mediates inflammation in the colon. Here, we investigated the effects of estradiol and progesterone in dextran sulphate sodium-induced colitis, using sham-operated or ovariectomized female mice with or without hormonal supplementation initiated three weeks before inflammation. We found that sham-operated, or ovariectomized mice supplemented either with only estradiol or estradiol and progesterone exhibited more severe intestinal inflammation compared to ovariectomized mice at day 7 of colitis. Simultaneously, progesterone supplementation of ovariectomized mice did not affect the inflammatory status. Estrogen receptors were expressed in several different cell types of the colonic mucosa, although at low levels. The estrogen receptor \u03b1 was observed in the epithelium as well as in mononuclear phagocytes and T and B cells. The estrogen receptor \u03b2 was found in the epithelium, and the G protein-coupled estrogen receptor in the\n                    <jats:italic>lamina propria<\/jats:italic>\n                    and vessel structures. Further, hormone depletion increased homeostatic immune cells, while estradiol exposure altered the expression of 791 genes involved in pathways promoting the antimicrobial response, immune cell activation, and metabolism related to epithelial integrity. With our results, we are the first to present strong and detailed evidence of estradiol as an inflammatory agent in the colon of female mice when allowing the appearance of longer-term effects.\n                  <\/jats:p>","DOI":"10.1007\/s10753-026-02554-y","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T16:20:59Z","timestamp":1783009259000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pre-Treatment with Estradiol, But not Progesterone, Exacerbates DSS Colitis: Dysregulated Innate Immunity and Impaired Epithelial Damage Response"],"prefix":"10.1007","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8039-8535","authenticated-orcid":false,"given":"Anja","family":"Hjelt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauri","family":"Polari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heli","family":"Jokela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pia","family":"Rantakari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heidi","family":"Gerke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M.","family":"Toivola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claes","family":"Ohlsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Poutanen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8752-6862","authenticated-orcid":false,"given":"Jorma","family":"M\u00e4\u00e4tt\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"2554_CR1","doi-asserted-by":"publisher","unstructured":"Chang, John T. 2020. Pathophysiology of Inflammatory Bowel Diseases. Edited by Dan L. Longo. New England Journal of Medicine 383. Massachusetts Medical Society: 2652\u20132664. https:\/\/doi.org\/10.1056\/NEJMRA2002697","DOI":"10.1056\/NEJMRA2002697"},{"key":"2554_CR2","doi-asserted-by":"publisher","unstructured":"Ortizo, Ronald, Stephanie Y. Lee, Emily T. Nguyen, Mohammad Mazen Jamal, Matthew M. Bechtold, and Douglas L. Nguyen. 2017. Exposure to oral contraceptives increases the risk for development of inflammatory bowel disease: A meta-analysis of case-controlled and cohort studies. European Journal of Gastroenterology and Hepatology 29 Lippincott Williams and Wilkins 1064\u20131070. https:\/\/doi.org\/10.1097\/MEG.0000000000000915","DOI":"10.1097\/MEG.0000000000000915"},{"key":"2554_CR3","doi-asserted-by":"publisher","unstructured":"Pasvol, Thomas Joshua, Stuart Bloom, Walter Anthony, Greta Segal, and Rait. 2022. and Laura Horsfall. Use of contraceptives and risk of inflammatory bowel disease: a nested case-control study Summary Background: How contraceptive formulation, dose, duration of therapy and mode. Alimentary Pharmacology & Therapeutics 55: 318\u2013326. https:\/\/doi.org\/10.1111\/apt.16647","DOI":"10.1111\/apt.16647"},{"key":"2554_CR4","doi-asserted-by":"publisher","unstructured":"Wang, Rui, Zhaoqi Li, Shaojun Liu, and Decai Zhang. 2023. Global, regional and national burden of inflammatory bowel disease in 204 countries and territories from 1990 to 2019: a systematic analysis based on the Global Burden of Disease Study 2019. BMJ Open 13 British Medical Journal Publishing Group e065186. https:\/\/doi.org\/10.1136\/bmjopen-2022-065186","DOI":"10.1136\/bmjopen-2022-065186"},{"key":"2554_CR5","doi-asserted-by":"publisher","unstructured":"Shah, Shailja C., Hamed Khalili, Corinne Gower-Rousseau, Ola Olen, Eric I. Benchimol, Elsebeth Lynge, and K\u00e1ri R. Nielsen et al. 2018. 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