{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T18:17:54Z","timestamp":1767809874825,"version":"3.49.0"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,5,27]],"date-time":"2021-05-27T00:00:00Z","timestamp":1622073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Urocortins (UCNs), belonging to corticotropin-releasing hormone (CRH) family, exert their function via CRH receptor type 1 (CRHR1) and 2 (CRHR2). Our previous studies have demonstrated that CRH acts on CRHR1 to potentiate prostaglandins (PGs) output induced by inflammatory stimuli in myometrial cells. In the present study, we sought to investigate the effects of UCNs on prostaglandin (PG) output via CRHR2 in cultured human uterine smooth muscle cells (HUSMCs) from pregnant women at term. We found that UCN and UCN 3 treatment promoted PGE2 and PGF2\u03b1 secretion in a dose-dependent manner. In contrast, UCN2 dose-dependently inhibited PGE2 and PGF2\u03b1 secretion. Their effects were reversed by CRHR2 antagonist and CRHR2 siRNA. Mechanically, we showed that UCN and UCN3 suppressed cAMP production and led to Gi activation while UCN2 stimulated cAMP production and activated Gs signaling. Further, UCN and UCN3 but not UCN2 activated NF-\u03baB and MAPK signaling pathways through Gi signaling. UCN and UCN3 stimulation of PGs secretion were dependent on Gi\/adenylyl cyclase (AC)\/cAMP, NF-\u03baB and MAPK signaling pathways. UCN2 suppression of PGs output was through Gs\/AC\/cAMP signaling pathways. Our data suggest that UCN, UCN2 and UCN3 can finely regulate PGs secretion via CRHR2, which facilitates the functional status of the uterus during pregnancy.<\/jats:p>","DOI":"10.1530\/rep-20-0659","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T09:20:45Z","timestamp":1619774445000},"page":"11-20","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":9,"title":["Urocortins exhibit differential effects on PGE2 and PGF2\u03b1 output via CRHR2 in human myometrium"],"prefix":"10.1093","volume":"162","author":[{"given":"Xingji","family":"You","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics and Research Center for Molecular Metabolomics , Xiangya Hospital Central South University, Changsha, China"},{"name":"Department of Physiology , Navy Medical University, Shanghai, China"},{"name":"Medical School of Shanghai University , Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zixi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology , Navy Medical University, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianqian","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics , Changhai Hospital, Shanghai, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruojin","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics and Research Center for Molecular Metabolomics , Xiangya Hospital Central South University, Changsha, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics , Changhai Hospital, Shanghai, 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