{"paper_id":"09f404c2-f72c-4768-8693-6878295f6923","body_text":"Abstract\nBackground\nSeveral studies suggest that resistance to progesterone may contribute to the pathophysiology of endometriosis. Progesterone mediates its biological activity via the 2 progesterone receptor (PR) isoforms (PR-A and PR-B). Effects of progesterone are determined by the PR-A:PR-B ratio such that a PR-B-dominant state promotes progesterone signaling, whereas a PR-A-dominant state decreases progesterone responsiveness. Our objective was to compare the abundance and cellular localization of the PR isoforms in endometrium and endometriotic lesions from women with and without peritoneal and ovarian endometriosis.\nMethods\nThis in vitro study was conducted in a tertiary care facility. Reproductive-age women with surgically diagnosed endometriosis (n = 18) and asymptomatic control individuals (n = 20) were prospectively recruited at the late proliferative and the early secretory phases. At laparoscopy, samples of eutopic endometrium, peritoneal and ovarian endometriosis, and disease-free peritoneum were obtained for subsequent immunohistochemical and immunoblot analysis of PR-B and total PR localization and PR-A and PR-B abundance, respectively.\nResults\nThe PR-A and PR-B were detected in eutopic endometrium and in peritoneal and ovarian endometriosis but not in disease-free peritoneum from patients with and without endometriosis. In peritoneal endometriosis, PR-A was the predominant isoform detected, whereas both receptors were detected in ovarian endometriosis and eutopic endometrium. In eutopic endometrium, levels of PR-A were significantly elevated in women with endometriosis compared with women without disease, regardless of menstrual phase. The PR-A levels were significantly elevated in ovarian endometriosis compared with peritoneal endometriosis.\nConclusions\nEndometriotic lesions and eutopic endometrium from women with endometriosis are uniform in a PR-A-dominant state. The data suggest that menstrual efflux of a PR-A-dominant endometrial tissue into the peritoneal cavity may play a role in the pathophysiology of endometriosis.\nSimilar content being viewed by others\nReferences\nSampson JA. Metastatic or embolic endometriosis, due to the menstrual dissemination of endometrial tissue into the venous circulation. Am J Pathol. 1927;3(2):93–110.43.\nEskenazi B, Warner ML. Epidemiology of endometriosis. Obstet Gynecol Clin North Am. 1997;24(2):235–258.\nKaunitz AM. Injectable depot medroxyprogesterone acetate contraception: an update for U.S. clinicians. Int J Fertil Womens Med. 1998;43(2):73–83.\nAttia GR, Zeitoun K, Edwards D, Johns A, Carr BR, Bulun SE. 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Abundance and Localization of Progesterone Receptor Isoforms in Endometrium in Women With and Without Endometriosis and in Peritoneal and Ovarian Endometriotic Implants. Reprod. Sci. 22, 1153–1161 (2015). https://doi.org/10.1177/1933719115585145\nPublished:\nIssue date:\nDOI: https://doi.org/10.1177/1933719115585145","source_license":"CC0","license_restricted":false}