{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:12:19Z","timestamp":1789733539569,"version":"4.0.1"},"reference-count":44,"publisher":"The Endocrine Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Endometriosis is an estrogen-dependent neurovascular disorder characterized by growth of endometrial tissue (lesions) outside the uterine cavity. Patients suffer chronic pelvic pain, and it has been proposed that co-recruitment of nerves\/blood vessels (neuroangiogenesis) into the lesions is fundamental to the development of painful symptoms. We hypothesized that estrogen-dependent regulation of axonal guidance molecules of the SLIT\/ROBO (Roundabout) family could play a role in neuroangiogenesis occurring in endometriosis lesions found on the peritoneal wall. In tissue samples from human patients and a mouse model of endometriosis, concentrations of mRNA encoded by SLIT3 were significantly higher in lesions than normal peritoneum. Estrogen regulation of SLIT3 was investigated using 17\u03b2-estradiol and selective agonists for each subtype of estrogen receptor (ER) (ER\u03b1 agonist, 4,4\u2032,4\u2033-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol; ER\u03b2 agonist, 2,3-bis(4-hydroxy-phenyl)-propionitrile [DPN]). In mice, DPN (EC50 0.85) increased Slit3 mRNA concentrations compared with hormone-depleted and 17\u03b2-estradiol-treated (EC50 0.1) animals and decreased the density of nerves but not vessels in endometriosis lesions. SLIT3 mRNA concentrations were increased in DPN-treated human endometrial endothelial cells and in 4,4\u2032,4\u2033-(4-propyl-(1H)-pyrazole-1,3,5-tryl) trisphenol-treated (EC50 200) rat dorsal root ganglia neurons. Functional assays (neurite outgrowth, network formation) revealed that SLIT3 promotes angiogenesis but decreases neurogenesis. In conclusion, these data suggest that estrogen-dependent expression of SLIT3 may play a key role in regulating nerve-vessel interactions within the complex microenvironment of endometriosis lesions.<\/jats:p>","DOI":"10.1210\/en.2014-1086","type":"journal-article","created":{"date-parts":[[2014,7,22]],"date-time":"2014-07-22T17:27:33Z","timestamp":1406050053000},"page":"4015-4026","source":"Crossref","is-referenced-by-count":73,"title":["Estrogen Receptor (ER) Agonists Differentially Regulate Neuroangiogenesis in Peritoneal Endometriosis via the Repellent Factor SLIT3"],"prefix":"10.1210","volume":"155","author":[{"given":"Erin","family":"Greaves","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Collins","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arantza","family":"Esnal-Zufiaurre","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevasti","family":"Giakoumelou","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew W.","family":"Horne","sequence":"first","affiliation":[{"name":"Medical Research Council Centre for Reproductive Health, The University of Edinburgh, Queens Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa T. 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