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The mechanism by which human labour is initiated in the presence of elevated circulating progesterone has remained an enigma since Csapo first theorized of a functional withdrawal of progesterone in 1965. Here we report that\n                    <jats:italic>in vitro<\/jats:italic>\n                    progesterone-liganded nuclear PRB forms a complex including JUN\/JUN homodimers and P54\n                    <jats:sup>nrb<\/jats:sup>\n                    \/Sin3A\/HDAC to repress transcription of the key labour gene,\n                    <jats:italic>Cx43<\/jats:italic>\n                    . In contrast, unliganded PRA paradoxically activates Cx43 transcription by interacting with FRA2\/JUND heterodimers. Furthermore, we find that while nuclear progesterone receptor (PR) is liganded during human pregnancy, it becomes unliganded during both term and preterm labour as a result of increased expression of the progesterone-metabolizing enzyme 20\u03b1 HSD and reduced nuclear progesterone levels. Our data provide a mechanism by which human labour can occur in the presence of elevated circulating progesterone and suggests non-metabolizable progestogen might represent an alternative new therapeutic approach to preterm birth prevention.\n                  <\/jats:p>","DOI":"10.1038\/ncomms11565","type":"journal-article","created":{"date-parts":[[2016,5,25]],"date-time":"2016-05-25T06:48:38Z","timestamp":1464158918000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":171,"title":["Molecular evidence of functional progesterone withdrawal in human myometrium"],"prefix":"10.1038","volume":"7","author":[{"given":"Lubna","family":"Nadeem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oksana","family":"Shynlova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elzbieta","family":"Matysiak-Zablocki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sam","family":"Mesiano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuesen","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Lye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,25]]},"reference":[{"key":"BFncomms11565_CR1","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1152\/ajplegacy.1929.88.2.326","volume":"88","author":"GW Corner","year":"1929","unstructured":"Corner, G. 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