{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T22:30:18Z","timestamp":1785364218423,"version":"3.55.0"},"reference-count":48,"publisher":"The Endocrine Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Oxytocin receptor (OTR) expression is increased before the onset of labor in all models of parturition. However, the mechanisms responsible for the increase in OTR expression are uncertain. Animal data suggest that uterine stretch increases OTR mRNA expression. In primary cultures of human uterine smooth muscle cells obtained from nonpregnant (NP) women and pregnant women before (NL) and after (L) the onset of labor, we investigated the effect of stretch on the expression of OTR mRNA and DNA binding of activator protein-1 (AP-1), CCAAT\/enhancer binding protein (C\/EBP)\u03b2, and nuclear factor-\u03baB transcription factors. OTR expression was least in NL, intermediate in NP, and greatest in L cells. Stretch of NL cells resulted in up-regulation of OTR mRNA expression associated with increased OTR gene promoter activity. Stretch of NP and L cells did not affect OTR mRNA expression. The increased promoter activity was associated with increased DNA binding of C\/EBP and AP-1 but not nuclear factor-\u03baB transcription factors. Overexpression of C\/EBP, but not AP-1, increased OTR promoter activity. We conclude that stretch of NL cells results in increased OTR mRNA expression probably through increased C\/EBP\u03b2 DNA binding. These data suggest that stretch contributes to the massive increase in OTR expression before the onset of human labor.<\/jats:p>","DOI":"10.1210\/jc.2004-0277","type":"journal-article","created":{"date-parts":[[2005,1,10]],"date-time":"2005-01-10T23:18:48Z","timestamp":1105399128000},"page":"237-246","source":"Crossref","is-referenced-by-count":91,"title":["Mechanical Stretch Up-Regulates the Human Oxytocin Receptor in Primary Human Uterine Myocytes"],"prefix":"10.1210","volume":"90","author":[{"given":"Vasso","family":"Terzidou","sequence":"first","affiliation":[{"name":"Imperial College Parturition Research Group (V.T., P.R.B.), Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, London W12 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suren R.","family":"Sooranna","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology (S.R.S., L.U.K., M.R.J.), Imperial College School of Medicine, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise U.","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology (S.R.S., L.U.K., M.R.J.), Imperial College School of Medicine, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Thornton","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences (S.T.), University of Warwick, Coventry CV4 7AL, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phillip R.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Imperial College Parturition Research Group (V.T., P.R.B.), Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, London W12 0NN, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology (S.R.S., L.U.K., M.R.J.), Imperial College School of Medicine, Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071620002414100_R1","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1067\/mob.2000.105816","article-title":"Maintenance treatment of preterm labor with the oxytocin antagonist atosiban. The Atosiban PTL-098 Study Group.","volume":"182","author":"Valenzuela","year":"2000","journal-title":"Am J Obstet Gynecol"},{"key":"2020071620002414100_R2","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1067\/mob.2000.95834","article-title":"An oxytocin receptor antagonist (atosiban) in the treatment of preterm labor: a randomized, double-blind, placebo-controlled trial with tocolytic rescue.","volume":"182","author":"Romero","year":"2000","journal-title":"Am J Obstet Gynecol"},{"key":"2020071620002414100_R3","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1210\/endo.137.2.8593830","article-title":"Expression of oxytocin receptor in human pregnant myometrium.","volume":"137","author":"Kimura","year":"1996","journal-title":"Endocrinology"},{"key":"2020071620002414100_R4","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1016\/0002-9378(84)90677-X","article-title":"Oxytocin receptors in the human uterus during pregnancy and parturition.","volume":"150","author":"Fuchs","year":"1984","journal-title":"Am J Obstet Gynecol"},{"key":"2020071620002414100_R5","doi-asserted-by":"crossref","first-page":"32451","DOI":"10.1016\/S0021-9258(18)31656-9","article-title":"Structural organization of the human oxytocin receptor gene.","volume":"269","author":"Inoue","year":"1994","journal-title":"J Biol Chem"},{"key":"2020071620002414100_R6","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0303-7207(98)00225-1","article-title":"Differential protein-DNA binding analysis identifies a novel enhancer element, US-1, involved in the up-regulation of the oxytocin receptor gene in human myometrium at term.","volume":"148","author":"Kimura","year":"1999","journal-title":"Mol Cell Endocrinol"},{"key":"2020071620002414100_R7","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1095\/biolreprod56.1.200","article-title":"Evidence for a local fetal influence on myometrial oxytocin receptors during pregnancy in the tammar wallaby (Macropus eugenii).","volume":"56","author":"Parry","year":"1997","journal-title":"Biol Reprod"},{"key":"2020071620002414100_R8","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1095\/biolreprod59.5.1055","article-title":"Increased expression of the rat myometrial oxytocin receptor messenger ribonucleic acid during labor requires both mechanical and hormonal signals.","volume":"59","author":"Ou","year":"1998","journal-title":"Biol Reprod"},{"key":"2020071620002414100_R9","doi-asserted-by":"crossref","first-page":"5712","DOI":"10.1210\/endo.140.12.7201","article-title":"Differential expression of myometrial oxytocin receptor and prostaglandin H synthase 2, but not estrogen receptor \u03b1 and heat shock protein 90 messenger ribonucleic acid in the gravid horn and nongravid horn in sheep during betamethasone-induced labor.","volume":"140","author":"Wu","year":"1999","journal-title":"Endocrinology"},{"key":"2020071620002414100_R10","first-page":"56","article-title":"Maternal serum concentrations of human placental lactogen, estradiol and pregnancy specific \u03b21-glycoprotein and fetal growth retardation.","volume":"165","author":"Gardner","year":"1997","journal-title":"Acta Obstet Gynecol Scand Suppl"},{"key":"2020071620002414100_R11","first-page":"117","article-title":"Polyhydramnion. A clinical study.","volume":"67","author":"Kirkinen","year":"1978","journal-title":"Ann Chir Gynaecol"},{"key":"2020071620002414100_R12","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1067\/mob.2001.111719","article-title":"The risks of spontaneous preterm delivery and perinatal mortality in relation to size at birth according to fetal versus neonatal growth standards.","volume":"184","author":"Lackman","year":"2001","journal-title":"Am J Obstet Gynecol"},{"key":"2020071620002414100_R13","first-page":"63","article-title":"Initiation of uterine contractions by purely mechanical stretching of the uterus at midpregnancy.","volume":"2","author":"Manabe","year":"1981","journal-title":"Int J Biol Res Pregnancy"},{"key":"2020071620002414100_R14","doi-asserted-by":"crossref","first-page":"279","DOI":"10.3109\/00016348209156572","article-title":"Stretch-induced cervical softening and initiation of labor at term. A possible correlation with prostaglandins.","volume":"61","author":"Manabe","year":"1982","journal-title":"Acta Obstet Gynecol Scand"},{"key":"2020071620002414100_R15","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1067\/mob.2002.122415","article-title":"Regulation of c-fos expression by static stretch in rat myometrial smooth muscle cells.","volume":"186","author":"Shynlova","year":"2002","journal-title":"Am J Obstet Gynecol"},{"key":"2020071620002414100_R16","doi-asserted-by":"crossref","first-page":"C1530","DOI":"10.1152\/ajpcell.00607.2001","article-title":"Mitogen-activated protein kinases mediate stretch-induced c-fos mRNA expression in myometrial smooth muscle cells","volume":"283","author":"Oldenhof","year":"2002","journal-title":"Am J Physiol Cell Physiol"},{"key":"2020071620002414100_R17","doi-asserted-by":"crossref","first-page":"18868","DOI":"10.1074\/jbc.M212777200","article-title":"CCAAT\/enhancer-binding protein and activator protein-1 transcription factors regulate the expression of interleukin-8 through the mitogen-activated protein kinase pathways in response to mechanical stretch of human airway smooth muscle cells.","volume":"278","author":"Kumar","year":"2003","journal-title":"J Biol Chem"},{"key":"2020071620002414100_R18","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/S0006-291X(03)01362-7","article-title":"Stretch-induced IL-6 secretion from endothelial cells requires NF-\u03baB activation.","volume":"308","author":"Kobayashi","year":"2003","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071620002414100_R19","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1093\/molehr\/gah021","article-title":"Mechanical stretch activates type 2 cyclooxygenase via activator protein-1 transcription factor in human myometrial cells.","volume":"10","author":"Sooranna","year":"2004","journal-title":"Mol Hum Reprod"},{"key":"2020071620002414100_R20","unstructured":"Binghui L 1992 Gel shift analysis with human recombinant AP1(c-jun): the effect of poly d(I-C) on specific complex formation. Promega Notes 14"},{"key":"2020071620002414100_R21","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1677\/joe.0.1610143","article-title":"Oxytocin receptor expression in human term and preterm gestational tissues prior to and following the onset of labour.","volume":"161","author":"Wathes","year":"1999","journal-title":"J Endocrinol"},{"key":"2020071620002414100_R22","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1210\/jcem.87.6.8609","article-title":"Progesterone withdrawal and estrogen activation in human parturition are coordinated by progesterone receptor A expression in the myometrium.","volume":"87","author":"Mesiano","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071620002414100_R23","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1016\/S0002-9378(98)70027-4","article-title":"Oxytocin and vasopressin 1a receptor gene expression in the cycling or pregnant human uterus.","volume":"179","author":"Helmer","year":"1998","journal-title":"Am J Obstet Gynecol"},{"key":"2020071620002414100_R24","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1095\/biolreprod66.5.1237","article-title":"Up-regulation of mesotocin receptors in the tammar wallaby myometrium is pregnancy-specific and independent of estrogen.","volume":"66","author":"Siebel","year":"2002","journal-title":"Biol Reprod"},{"key":"2020071620002414100_R25","doi-asserted-by":"crossref","first-page":"3213","DOI":"10.1210\/endo.137.8.8754742","article-title":"Relationships among sex steroids, oxytocin, and their receptors in the rat uterus during late gestation and at parturition.","volume":"137","author":"Fang","year":"1996","journal-title":"Endocrinology"},{"key":"2020071620002414100_R26","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1210\/endo.138.7.5247","article-title":"Effects of RU486 on estrogen, progesterone, oxytocin, and their receptors in the rat uterus during late gestation.","volume":"138","author":"Fang","year":"1997","journal-title":"Endocrinology"},{"key":"2020071620002414100_R27","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1210\/endo.139.6.6030","article-title":"Ontogeny of oxytocin receptors and oxytocin-induced stimulation of prostaglandin synthesis in prepubertal heifers.","volume":"139","author":"Fuchs","year":"1998","journal-title":"Endocrinology"},{"key":"2020071620002414100_R28","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1113\/eph8602185","article-title":"The structure and regulation of the oxytocin receptor.","volume":"86","author":"Ivell","year":"2001","journal-title":"Exp Physiol"},{"key":"2020071620002414100_R29","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1139\/o83-078","article-title":"Regulation of oxytocin receptor concentration in rat uterine explants by estrogen and progesterone.","volume":"61","author":"Soloff","year":"1983","journal-title":"Can J Biochem Cell Biol"},{"key":"2020071620002414100_R30","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1210\/endo.138.3.4998","article-title":"Cloning, novel promoter sequence, and estrogen regulation of a rat oxytocin receptor gene.","volume":"138","author":"Bale","year":"1997","journal-title":"Endocrinology"},{"key":"2020071620002414100_R31","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1046\/j.1439-0531.2000.00226.x","article-title":"Regulation of the oxytocin receptor in bovine reproductive tissues and the role of steroids.","volume":"35","author":"Ivell","year":"2000","journal-title":"Reprod Domest Anim"},{"key":"2020071620002414100_R32","first-page":"127","article-title":"Parathyroid hormone-related protein mRNA in sheep endometrium and myometrium during late gestation and labor.","volume":"5","author":"Wu","year":"1998","journal-title":"J Soc Gynecol Investig"},{"key":"2020071620002414100_R33","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1095\/biolreprod.103.016014","article-title":"Parathyroid hormone-related protein treatment of pregnant rats delays the increase in connexin 43 and oxytocin receptor expression in the myometrium.","volume":"69","author":"Mitchell","year":"2003","journal-title":"Biol Reprod"},{"key":"2020071620002414100_R34","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1095\/biolreprod67.1.240","article-title":"Differential expression of activator protein-1 transcription factors in pregnant rat myometrium.","volume":"67","author":"Mitchell","year":"2002","journal-title":"Biol Reprod"},{"key":"2020071620002414100_R35","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/0021-9290(95)00096-8","article-title":"Cyclic strain causes heterogeneous induction of transcription factors, AP-1, CRE binding protein and NF-kB, in endothelial cells: species and vascular bed diversity.","volume":"28","author":"Du","year":"1995","journal-title":"J Biomech"},{"key":"2020071620002414100_R36","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1006\/bbrc.2001.5023","article-title":"MAPK and SRC-kinases control EGR-1 and NF-\u03baB inductions by changes in mechanical environment in osteoblasts.","volume":"284","author":"Granet","year":"2001","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071620002414100_R37","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1096\/fj.01-0354fje","article-title":"Uni-axial cyclic stretch induces the activation of transcription factor nuclear factor \u03baB in human fibroblast cells.","volume":"16","author":"Inoh","year":"2002","journal-title":"FASEB J"},{"key":"2020071620002414100_R38","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/j.8755-8920.2001.450305.x","article-title":"Interleukin-6 up-regulates the oxytocin receptor in cultured uterine smooth muscle cells.","volume":"45","author":"Rauk","year":"2001","journal-title":"Am J Reprod Immunol"},{"key":"2020071620002414100_R39","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.8755-8920.2000.440201.x","article-title":"Effects of LPS and IL-6 on oxytocin receptor in nonpregnant and pregnant rat uterus.","volume":"44","author":"Fang","year":"2000","journal-title":"Am J Reprod Immunol"},{"key":"2020071620002414100_R40","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S1071-5576(01)00142-3","article-title":"Production of oxytocin receptor and cytokines in primary uterine smooth muscle cells cultivated under inflammatory conditions.","volume":"9","author":"Helmer","year":"2002","journal-title":"J Soc Gynecol Investig"},{"key":"2020071620002414100_R41","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1210\/endo.142.4.8107","article-title":"Transcriptional regulation of oxytocin receptor by interleukin-1\u03b2 and interleukin-6.","volume":"142","author":"Schmid","year":"2001","journal-title":"Endocrinology"},{"key":"2020071620002414100_R42","doi-asserted-by":"crossref","first-page":"35668","DOI":"10.1074\/jbc.M305182200","article-title":"Subnuclear localization of C\/EBP\u03b2 is regulated by growth hormone and dependent on MAPK.","volume":"278","author":"Piwien Pilipuk","year":"2003","journal-title":"J Biol Chem"},{"key":"2020071620002414100_R43","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/jnci\/95.1.53","article-title":"Essential role of phosphatidylinositol 3-kinase-dependent CCAAT\/enhancer binding protein \u03b2 activation in the induction of glutathione S-transferase by oltipraz.","volume":"95","author":"Kang","year":"2003","journal-title":"J Natl Cancer Inst"},{"key":"2020071620002414100_R44","doi-asserted-by":"crossref","first-page":"23455","DOI":"10.1016\/S0021-9258(18)35857-5","article-title":"Stretch-induced parathyroid hormone-related peptide gene expression in the rat uterus.","volume":"267","author":"Daifotis","year":"1992","journal-title":"J Biol Chem"},{"key":"2020071620002414100_R45","doi-asserted-by":"crossref","first-page":"5398","DOI":"10.1210\/endo.138.12.5624","article-title":"Expression of connexin-43 and connexin-26 in the rat myometrium during pregnancy and labor is differentially regulated by mechanical and hormonal signals.","volume":"138","author":"Ou","year":"1997","journal-title":"Endocrinology"},{"key":"2020071620002414100_R46","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/S0002-9378(00)70347-4","article-title":"Expression and regulation of the messenger ribonucleic acid encoding the prostaglandin F(2\u03b1) receptor in the rat myometrium during pregnancy and labor.","volume":"182","author":"Ou","year":"2000","journal-title":"Am J Obstet Gynecol"},{"key":"2020071620002414100_R47","doi-asserted-by":"crossref","first-page":"5209","DOI":"10.1210\/jc.2002-020531","article-title":"Cyclic mechanical stretch augments prostacyclin production in cultured human uterine myometrial cells from pregnant women: possible involvement of up-regulation of prostacyclin synthase expression.","volume":"87","author":"Korita","year":"2002","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071620002414100_R48","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1093\/molehr\/gah112","volume":"10","author":"Loudon","journal-title":"Mol Hum Reprod"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/90\/1\/237\/10812309\/jcem0237.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/90\/1\/237\/10812309\/jcem0237.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T21:44:18Z","timestamp":1625348658000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/90\/1\/237\/3058064"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,1,1]]},"references-count":48,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,1,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2004-0277","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,1,1]]}}}