title: Negative Effects of SRD5A1 on Nuclear Activity of Progesterone Receptor Isoform B in JEG3 Cells.
abstract: Progesterone withdrawal signals labor in mammals. Elevated intracellular metabolism contributes to progesterone functional withdrawal through unknown mechanism, which is thought to act via progesterone receptor (PR). This study aims to investigate molecular mechanisms underlying progesterone withdrawal during pregnancy and labor. We investigated the role of 5α-reductase type I (SRD5A1) in enzymatic catalysis of progesterone and loss of PR function in a human trophoblast choriocarcinoma cell line JEG3. The PR isoform B (PR-B) was robustly expressed in JEG3 cells. The SRD5A1 small-interfering RNA knockdown led to significant increase in PR-B nuclear import, ectopic, whereas SRD5A1 overexpression resulted in remarkable inhibition of nuclear PR-B in P4-treated cells. Repression of SRD5A1 activated PR-B responsive gene, whereas overexpression of SRD5A1 possessed an inhibitory effect. JEG3 cell line is a valuable tool to study mechanisms responsible for loss of PR function and screening of drugs for preterm birth treatment. Our study aims to investigate the molecular mechanisms underlying progesterone withdrawal during pregnancy and labor.
authors.affiliation: Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shanxi, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Miao
authors.affiliation: Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shanxi, China.
authors.forename: Min
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shanxi, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shanxi, China yqyao2@163.com.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Department of Obstetrics and Gynecology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shanxi, China yili2223@163.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D011374:Progesterone / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone; C097314:progesterone receptor B; D011374:Progesterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548467:SRD5A1 protein, human
keywords: 5α-reductase type I; preterm birth; progesterone receptor; progesterone withdrawal; trophoblast choriocarcinoma