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This suggests that increased 20\u03b1-HSD activity is a mechanism through which inflammation drives progesterone withdrawal in preterm labor. In this study, we have determined the effects of various treatments of therapeutic relevance on\n                    <jats:italic>AKR1C1<\/jats:italic>\n                    expression in pregnant human myometrium in an ex vivo culture system.\n                    <jats:italic>AKR1C1<\/jats:italic>\n                    expression increased spontaneously during 48\u00a0h culture (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001), consistent with the myometrium transitioning to a labor-like phenotype ex vivo\n                    <jats:italic>,<\/jats:italic>\n                    as reported previously. Serum supplementation, prostaglandin F\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    , phorbol myristate acetate, and mechanical stretch had no effect on the culture-induced increase, whereas progesterone (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0058) and cAMP (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0202) further upregulated\n                    <jats:italic>AKR1C1<\/jats:italic>\n                    expression. In contrast, culture-induced upregulation of\n                    <jats:italic>AKR1C1<\/jats:italic>\n                    expression was dose-dependently repressed by three histone\/protein deacetylase inhibitors: trichostatin A at 5 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0172) and 25\u00a0\u00b5M (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0115); suberoylanilide hydroxamic acid at 0.5 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0070), 1 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0045), 2.5 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0181), 5 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0066) and 25\u00a0\u00b5M (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0014); and suberoyl bis-hydroxamic acid at 5 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0480) and 25\u00a0\u00b5M (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0238). We propose the inhibition of histone\/protein deacetylation helps to maintain the anti-inflammatory, pro-quiescence signaling of progesterone in pregnant human myometrium by blocking its metabolic inactivation. Histone deacetylase inhibitors may represent a class of agents that preserve or restore the progesterone sensitivity of the pregnant uterus.\n                  <\/jats:p>","DOI":"10.1007\/s43032-023-01333-6","type":"journal-article","created":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T15:01:41Z","timestamp":1693407701000},"page":"150-161","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Regulation of 20\u03b1-Hydroxysteroid Dehydrogenase Expression in Term Pregnant Human Myometrium Ex Vivo"],"prefix":"10.1007","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8647-9213","authenticated-orcid":false,"given":"Marina","family":"Paul","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5835-3309","authenticated-orcid":false,"given":"Anna Paredes","family":"Barreda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7627-1005","authenticated-orcid":false,"given":"Amy","family":"Gregson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-0659-1222","authenticated-orcid":false,"given":"Richard","family":"Kahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9637-940X","authenticated-orcid":false,"given":"Madeline","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5392-1880","authenticated-orcid":false,"given":"Waleed M.","family":"Hussein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9068-0761","authenticated-orcid":false,"given":"Frederick R.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4720-0280","authenticated-orcid":false,"given":"Roger","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1690-1159","authenticated-orcid":false,"given":"Tamas","family":"Zakar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3064-6358","authenticated-orcid":false,"given":"Jonathan W.","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,8,30]]},"reference":[{"issue":"3","key":"1333_CR1","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1111\/j.1600-0897.2007.00512.x","volume":"58","author":"P Arck","year":"2007","unstructured":"Arck P, Hansen PJ, Mulac Jericevic B, Piccinni MP, Szekeres-Bartho J. 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