{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T07:45:52Z","timestamp":1782546352209,"version":"3.54.5"},"reference-count":45,"publisher":"The Endocrine Society","issue":"7","license":[{"start":{"date-parts":[[2018,5,25]],"date-time":"2018-05-25T00:00:00Z","timestamp":1527206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Progesterone (P) resistance is a hallmark of endometriosis, but the underlying mechanism(s) for loss of P sensitivity leading to lesion establishment remains poorly understood.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To evaluate the association between Notch-1 signaling activation and P resistance in the progression of endometriosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Case control study; archived formalin-fixed, paraffin-embedded tissues.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>University hospitals (United States, Taiwan).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Patients<\/jats:title>\n                  <jats:p>Women with endometriosis; human endometrial stromal cell line (HESC).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Intervention<\/jats:title>\n                  <jats:p>Eutopic endometria (EU) and ectopic lesions (ECs) were collected from surgically diagnosed patients. Archived tissue sections of EU and ECs were identified. HESCs were treated with N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT) and valproic acid (VPA) to, respectively, suppress and induce Notch-1 activation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Outcome Measures<\/jats:title>\n                  <jats:p>Tissues were analyzed for Notch Intra-Cellular Domain 1 (NICD1) and progesterone receptor (PGR) protein expression by immunohistochemistry and for transcript levels of NICD1 target genes HES1, PGR, and PGR-B by quantitative reverse transcription polymerase chain reaction. DAPT- or VPA-treated HESCs with and without P cotreatment were evaluated for cell numbers and for PGR, HES1, and PGR target gene DKK1 transcript levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Nuclear-localized stromal NICD1 protein levels were inversely associated with those of total PGR in EU and ECs. Stromal ECs displayed higher HES1 and lower total PGR and PGR-B transcript levels than EU. In HESCs, DAPT reduction of NICD1 decreased cell numbers and increased PGR transcript and nuclear PGR protein levels and, with P cotreatment, maintained P sensitivity. Conversely, VPA induction of NICD1 decreased PGR transcript levels and, with P cotreatment, abrogated P-induced DKK1 and maintained HES1 transcript levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Aberrant Notch-1 activation is associated with decreased PGR that contributes to P resistance in endometriosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/js.2018-00007","type":"journal-article","created":{"date-parts":[[2018,5,25]],"date-time":"2018-05-25T18:08:35Z","timestamp":1527271715000},"page":"765-778","source":"Crossref","is-referenced-by-count":25,"title":["Notch-1 Signaling Activation and Progesterone Receptor Expression in Ectopic Lesions of Women With Endometriosis"],"prefix":"10.1210","volume":"2","author":[{"given":"Dustin M","family":"Brown","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiu-Chi","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Physiology, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles M","family":"Quick","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo M","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank A","family":"Simmen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaw-Jenq","family":"Tsai","sequence":"additional","affiliation":[{"name":"Department of Physiology, National Cheng Kung University, Tainan, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosalia C M","family":"Simmen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, 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