{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T18:42:27Z","timestamp":1771008147273,"version":"3.50.1"},"reference-count":42,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[1999,2,1]]},"abstract":"<jats:p> Although it is well known that progesterone alters uterine contractility and plays an important role in maintenance of pregnancy, the biochemical mechanisms by which progesterone alters uterine contractility in human gestation are less clear. In this investigation we sought to identify progesterone-induced adaptations in human myometrial smooth muscle cells that may alter Ca<jats:sup>2+<\/jats:sup>signaling in response to contractile agents. Cells were treated with vehicle or the progesterone analog medroxyprogesterone acetate (MPA) for 5 days, and intracellular free Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) was quantified after treatment with oxytocin (OX) or endothelin (ET)-1. OX- and ET-1-induced increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>were significantly attenuated in cells pretreated with MPA in a dose-dependent manner. Progesterone receptor antagonists prevented the attenuated Ca<jats:sup>2+<\/jats:sup> transients induced by MPA. ET<jats:sub>A<\/jats:sub> and ET<jats:sub>B<\/jats:sub> receptor subtypes were expressed in myometrial cells, and treatment with MPA resulted in significant downregulation of ET<jats:sub>A<\/jats:sub>and ET<jats:sub>B<\/jats:sub> receptor binding. MPA did not alter ionomycin-stimulated increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>and had no effect on inositol trisphosphate-dependent or -independent release of Ca<jats:sup>2+<\/jats:sup> from internal Ca<jats:sup>2+<\/jats:sup> stores. We conclude that adaptations of Ca<jats:sup>2+<\/jats:sup> homeostasis in myometrial cells during pregnancy may include progesterone-induced modification of receptor-mediated increases in [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>. <\/jats:p>","DOI":"10.1152\/ajpcell.1999.276.2.c379","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T22:24:23Z","timestamp":1514154263000},"page":"C379-C385","source":"Crossref","is-referenced-by-count":41,"title":["Effect of progesterone on intracellular Ca<sup>2+<\/sup> homeostasis  in human myometrial smooth muscle cells"],"prefix":"10.1152","volume":"276","author":[{"given":"Victor P.","family":"Fomin","sequence":"first","affiliation":[{"name":"Departments of Obstetrics and Gynecology and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blair E.","family":"Cox","sequence":"additional","affiliation":[{"name":"Pediatrics, University of Texas Southwestern Medical Center, Dallas, Texas 75235"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. 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