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We found that 20\u03b1\u2010HSD protein is significantly increased in human myometrium during term labour, and in mouse uterus during term and preterm labour. Treatment of human myometrial cells with the pro\u2010inflammatory mediators, lipopolysaccharide (LPS, mimicking infection) and 12\u2010O\u2010tetradecanoylphorbol\u201013\u2010acetate (TPA, mimicking inflammation), induced 20\u03b1\u2010HSD gene expression and increased 20\u03b1\u2010HSD protein abundance. LPS treatment decreased P4 release into the culture medium and resulted in up\u2010regulation of GJA1 in the hTERT\u2010HM cells. The NF\u2010\u043aB \/AP\u20101 transcription factors mediated effects of LPS and TPA on 20\u03b1\u2010HSD gene transcription. Both pro\u2010inflammatory stimuli induced 20\u03b1\u2010HSD promoter activity in LPS\/TPA\u2010treated cells which was significantly attenuated by inhibition of NF\u2010\u043aB (JSH: 20\u00a0\u00b5M) or AP\u20101 signalling (T5224: 10\u00a0\u00b5M). Deletion of NF\u2010\u043aB consensus sites abrogated LPS\u2010mediated promoter induction, while removal of AP\u20101 sites reversed the TPA\u2010mediated induction of 20\u03b1\u2010HSD promoter. We conclude that inflammatory stimuli (physiologic or pathologic) that activate NF\u2010\u043aB or AP\u20101 induce 20\u03b1\u2010HSD transcription and subsequent local P4 withdrawal resulting in up\u2010regulation of GJA1 and activation of myometrium that precedes labour.<\/jats:p>","DOI":"10.1111\/jcmm.16681","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T02:40:56Z","timestamp":1623379256000},"page":"6773-6785","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Pro\u2010inflammatory signals induce 20\u03b1\u2010HSD expression in myometrial cells: A key mechanism for local progesterone withdrawal"],"prefix":"10.1111","volume":"25","author":[{"given":"Lubna","family":"Nadeem","sequence":"first","affiliation":[{"name":"Lunenfeld Tanenbaum Research Institute Mount Sinai Hospital Toronto ON 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