{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T22:51:14Z","timestamp":1787784674045,"version":"build-2784847793"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Innovation and Technology","award":["TKP2021-EGA-32"],"award-info":[{"award-number":["TKP2021-EGA-32"]}]},{"name":"Stipendium Hungaricum Scholarship, University of Szeged, Hungary"},{"name":"Stipendium Hungaricum Scholarship, University of Szeged, Hungary"},{"name":"Stipendium Hungaricum Scholarship, University of Szeged, Hungary"},{"name":"Research Fund of Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Hungary"},{"DOI":"10.13039\/501100015763","name":"University of Szeged","doi-asserted-by":"crossref","award":["Open Access Fund 8261"],"award-info":[{"award-number":["Open Access Fund 8261"]}],"id":[{"id":"10.13039\/501100015763","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    This study aimed to investigate the non-genomic effect of testosterone (T) on uterine muscle contractility in non-pregnant and 22\n                    <jats:sup>nd<\/jats:sup>\n                    day pregnant rats, in vivo. It provides the first evidence of an in vivo T uterine relaxation effect during pregnancy. Circulating T levels were measured within 8 hours after a single intraperitoneal (ip) administration of T (10 mg\/kg) by ELISA. The kinetic curves of a single dose of T (10 mg\/kg of ip) were estimated for 8 hours; plasma T was measured using ELISA kits. The rapid in vivo action of T was studied by measuring contractions using strain-gauge sensors in 15-minute intervals, and the AUC was calculated. The animals received T alone (3\/10\/30\/100\/300 mg\/kg ip), with flutamide (100 mg\/kg ip), solvent (DMSO+Macrogol 25%\u2009+\u200975%, 1 ml\/kg ip) or normal saline (1 ml\/kg) (n\u2009=\u20095\u20138\/group, 160\u2013220 g). To verify the possible mechanism of action, we also examined the uterine relaxing effect of T (10\n                    <jats:sup>\u22124<\/jats:sup>\n                    M) and nifedipine (10\n                    <jats:sup>\u22127<\/jats:sup>\n                    M) in vitro on KCl (40 mM)-stimulated contractions by cumulatively increasing the concentration of CaCl\n                    <jats:sub>2<\/jats:sub>\n                    (1\u2013120 mM) in the organ bath. Plasma T and 4-hydroxyphenylpyruvate dioxygenase (4-HPPD) levels were measured by ELISA before and 30-minutes after administration (n\u2009=\u20094\u20138\/group, 200\u2013220 g). T had similar half-life and t\n                    <jats:sub>max<\/jats:sub>\n                    values in both non-pregnant and pregnant rats, however, the AUC values were higher in pregnant animals. T (30\/100\/300 mg\/kg single ip dose) elicited a flutamide-resistant dose-dependent uterine relaxing effect in both non-pregnant and 22\n                    <jats:sup>nd<\/jats:sup>\n                    day pregnant rats. T plasma levels were proportional with the administered doses. 4-HPPD plasma levels remained unchanged in both non-pregnant and 22\n                    <jats:sup>nd<\/jats:sup>\n                    day pregnant rats after 30 min of T administration. A single dose T induces rapid, non-genomic, dose-dependent uterine relaxation via blocking of calcium effect in non-pregnant and late-pregnant rats in vivo. Based on our results, T or its analogues might be good candidates for further pre-clinical and clinical studies for uterine hyperactivity-related conditions.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0348344","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T17:38:42Z","timestamp":1778002722000},"page":"e0348344","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Testosterone reduces uterine contractions in vivo: Evidence for non-genomic action in rats"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6033-653X","authenticated-orcid":true,"given":"Saif-alnasr H.","family":"Mohammed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0401-6380","authenticated-orcid":true,"given":"Mohammed","family":"Taj-Eldin Abdalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4271-3882","authenticated-orcid":true,"given":"Ayman B.","family":"Mousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9836-1431","authenticated-orcid":true,"given":"Anita","family":"Sztojkov-Ivanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5878-4691","authenticated-orcid":true,"given":"K\u00e1lm\u00e1n Ferenc","family":"Sz\u0171cs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1571-7579","authenticated-orcid":true,"given":"R\u00f3bert","family":"G\u00e1sp\u00e1r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"issue":"3","key":"pone.0348344.ref001","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1055\/s-2007-973430","article-title":"Non-genomic sex steroid actions in the vascular system","volume":"25","author":"X-D Fu","year":"2007","journal-title":"Semin Reprod Med"},{"issue":"13","key":"pone.0348344.ref002","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1042\/CS20170090","article-title":"Genomic and non-genomic effects of androgens in the cardiovascular system: clinical implications","volume":"131","author":"AK Lucas-Herald","year":"2017","journal-title":"Clin Sci"},{"key":"pone.0348344.ref003","doi-asserted-by":"crossref","first-page":"118584","DOI":"10.1016\/j.lfs.2020.118584","article-title":"Non-genomic actions of sex hormones on pregnant uterine contractility in rats: An in vitro study at term","volume":"263","author":"M Mirdamadi","year":"2020","journal-title":"Life Sci"},{"key":"pone.0348344.ref004","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/978-3-030-68748-9_15","article-title":"Sex Hormones and Lung Inflammation","volume":"1304","author":"J Reyes-Garc\u00eda","year":"2021","journal-title":"Adv Exp Med Biol"},{"issue":"5","key":"pone.0348344.ref005","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1172\/JCI125755","article-title":"Impact of estrogens in males and androgens in females","volume":"129","author":"SR Hammes","year":"2019","journal-title":"J Clin 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