{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:19:44Z","timestamp":1791159584194,"version":"4.1.0"},"reference-count":32,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Context: Experimental and clinical studies in a variety of nonprimate species demonstrate that progesterone withdrawal leads to changes in gene expression that initiate parturition at term. Mice deficient in 5\u03b1-reductase type I fail to undergo cervical ripening at term despite the timely onset of luteolysis and progesterone withdrawal in blood.<\/jats:p><jats:p>Objective: Our objective was to test the hypothesis that estrogen and progesterone metabolism is regulated in cervical tissues during pregnancy, even in species in which parturition is not characterized by progesterone withdrawal in blood.<\/jats:p><jats:p>Design: Estradiol and progesterone metabolism was quantified in intact cervical tissues from nonpregnant and pregnant women at term before or after labor.<\/jats:p><jats:p>Setting: The study was conducted at a university hospital.<\/jats:p><jats:p>Patients: Tissues were obtained from five nonpregnant and 21 pregnant women (nine before labor and 12 in labor).<\/jats:p><jats:p>Main Outcome Measures: Enzyme activity measurements, Northern blot analysis, quantitative real-time RT-PCR, and immunohistochemistry were used to quantify steroid hormone metabolizing enzymes in cervical and myometrial tissues.<\/jats:p><jats:p>Results: During pregnancy, 17\u03b2-hydroxysteroid dehydrogenase type 2 was induced in glandular epithelial cells to catalyze the conversion of estradiol to estrone and stroma-derived 20\u03b1-hydroxyprogesterone to progesterone. During parturition, 17\u03b2-hydroxysteroid dehydrogenase type 2 was down-regulated in endocervical cells, thereby creating a microenvironment favorable for cervical ripening.<\/jats:p><jats:p>Conclusions: Together, the data indicate that cervical ripening during parturition involves localized regulation of estrogen and progesterone metabolism through a complex relationship between cervical epithelium and stroma, and that steroid hormone metabolism in cervical tissues from pregnant women is unique from that in mice.<\/jats:p>","DOI":"10.1210\/jc.2007-2813","type":"journal-article","created":{"date-parts":[[2008,3,26]],"date-time":"2008-03-26T00:25:11Z","timestamp":1206491111000},"page":"2366-2374","source":"Crossref","is-referenced-by-count":82,"title":["Estrogen and Progesterone Metabolism in the Cervix during Pregnancy and Parturition"],"prefix":"10.1210","volume":"93","author":[{"given":"Stefan","family":"Andersson","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Minjarez","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole P.","family":"Yost","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Ann","family":"Word","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9032"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071613393058000_R1","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1055\/s-2006-956777","article-title":"Dynamics of cervical remodeling during pregnancy and parturition: mechanisms and current concepts.","volume":"25","author":"Word","year":"2007","journal-title":"Semin Reprod Med"},{"key":"2020071613393058000_R2","first-page":"981","article-title":"The parturition defect in steroid 5\u03b1-reductase type 1 knockout mice is due to impaired cervical ripening.","volume":"13","author":"Mahendroo","year":"1999","journal-title":"Mol Endocrinol"},{"key":"2020071613393058000_R3","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":"2020071613393058000_R4","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1177\/1933719107302380","article-title":"Progesterone receptor or cytoskeletal protein?","volume":"14","author":"Madsen","year":"2007","journal-title":"Reprod Sci"},{"key":"2020071613393058000_R5","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.semcdb.2007.05.003","article-title":"Steroid hormone control of myometrial contractility and parturition.","volume":"18","author":"Mesiano","year":"2007","journal-title":"Semin Cell Dev Biol"},{"key":"2020071613393058000_R6","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1210\/jc.2003-031037","article-title":"Prostaglandins differentially modulate progesterone receptor-A and -B expression in human myometrial cells: evidence for prostaglandin-induced functional progesterone withdrawal.","volume":"89","author":"Madsen","year":"2004","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613393058000_R7","first-page":"119","article-title":"Progesterone control of cervical ripening\u2013experimental studies with the progesterone antagonists onapristone, lilopristone, and mifepristone","author":"Chwalisz","year":"1991","journal-title":"In: Leppert PC, Woessner Jr JF, eds. The extracellular matrix of the uterus, cervix, and fetal membranes, synthesis, degradation, and hormonal regulation. Ithaca, NY: Perinatology Press;"},{"key":"2020071613393058000_R8","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1210\/endo-128-2-863","article-title":"Hormonal regulation of interstitial collagenase in the uterine cervix of the pregnant guinea pig.","volume":"128","author":"Rajabi","year":"1991","journal-title":"Endocrinology"},{"key":"2020071613393058000_R9","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1210\/endo-128-1-371","article-title":"Immunochemical and immunohistochemical evidence of estrogen-mediated collagenolysis as a mechanism of cervical dilatation in the guinea pig at parturition.","volume":"128","author":"Rajabi","year":"1991","journal-title":"Endocrinology"},{"key":"2020071613393058000_R10","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1095\/biolreprod.104.032979","article-title":"Human myometrial gene expression before and during parturition.","volume":"72","author":"Havelock","year":"2005","journal-title":"Biol Reprod"},{"key":"2020071613393058000_R11","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.plefa.2003.04.009","article-title":"Prostaglandins and the myometrium and cervix.","volume":"70","author":"Hertelendy","year":"2004","journal-title":"Prostaglandins Leukot Essent Fatty Acids"},{"key":"2020071613393058000_R12","doi-asserted-by":"crossref","first-page":"12964","DOI":"10.1016\/S0021-9258(18)31480-7","article-title":"Expression cloning and characterization of human 17 beta-hydroxysteroid dehydrogenase type 2, a microsomal enzyme possessing 20 alpha-hydroxysteroid dehydrogenase activity.","volume":"268","author":"Wu","year":"1993","journal-title":"J Biol Chem"},{"key":"2020071613393058000_R13","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S1570-9639(02)00434-X","article-title":"Amino acid substitution of arginine 80 in 17beta-hydroxysteroid dehydrogenase type 3 and its effect on NADPH cofactor binding and oxidation\/reduction kinetics.","volume":"1601","author":"McKeever","year":"2002","journal-title":"Biochim Biophys Acta"},{"key":"2020071613393058000_R14","first-page":"3872","article-title":"Cell type-specific expression of 17 \u03b2-hydroxysteroid dehydrogenase type 2 in human placenta and fetal liver.","volume":"82","author":"Moghrabi","year":"1997","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613393058000_R15","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1073\/pnas.87.10.3640","article-title":"Structural and biochemical properties of cloned and expressed human and rat steroid 5 alpha-reductases.","volume":"87","author":"Andersson","year":"1990","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020071613393058000_R16","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1038\/354159a0","article-title":"Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism.","volume":"354","author":"Andersson","year":"1991","journal-title":"Nature"},{"issue":"Pt 1","key":"2020071613393058000_R17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1042\/bj3510067","article-title":"Human 3alpha-hydroxysteroid dehydrogenase isoforms (AKR1C1-AKR1C4) of the aldo-keto reductase superfamily: functional plasticity and tissue distribution reveals roles in the inactivation and formation of male and female sex hormones","volume":"351","author":"Penning","year":"2000","journal-title":"Biochem J"},{"key":"2020071613393058000_R18","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.mce.2005.10.024","article-title":"Deoxycorticosterone inactivation by AKR1C3 in human mineralocorticoid target tissues.","volume":"248","author":"Sharma","year":"2006","journal-title":"Mol Cell Endocrinol"},{"key":"2020071613393058000_R19","doi-asserted-by":"crossref","first-page":"1378","DOI":"10.1095\/biolreprod65.5.1378","article-title":"Regulation of uterine 5 alpha-reductase type 1 in mice.","volume":"65","author":"Minjarez","year":"2001","journal-title":"Biol Reprod"},{"issue":"Pt 1","key":"2020071613393058000_R20","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1042\/bj3010183","article-title":"Suppression of interleukin 8 production by progesterone in rabbit uterine cervix","volume":"301","author":"Ito","year":"1994","journal-title":"Biochem J"},{"key":"2020071613393058000_R21","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1046\/j.1469-0705.2000.00050.x","article-title":"The cervix as a predictor of preterm delivery in \u2018at-risk\u2019 women.","volume":"15","author":"Cook","year":"2000","journal-title":"Ultrasound Obstet Gynecol"},{"key":"2020071613393058000_R22","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/S0002-9378(11)90768-6","article-title":"Changes in 17 beta,20 alpha-hydroxysteroid dehydrogenase activity supporting an increase in the estrogen\/progesterone ratio of human fetal membranes at parturition.","volume":"168","author":"Mitchell","year":"1993","journal-title":"Am J Obstet Gynecol"},{"key":"2020071613393058000_R23","first-page":"598","volume-title":"Wien Klin Wochenschr","author":"Baumann","year":"1995"},{"key":"2020071613393058000_R24","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/0002-9378(93)90634-U","article-title":"Interleukin-8 production by the human cervix.","volume":"169","author":"Barclay","year":"1993","journal-title":"Am J Obstet Gynecol"},{"key":"2020071613393058000_R25","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.ajog.2004.03.023","article-title":"Matrix metalloproteinases and their inhibitors in the cervical mucus plug at term of pregnancy.","volume":"191","author":"Becher","year":"2004","journal-title":"Am J Obstet Gynecol"},{"key":"2020071613393058000_R26","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1093\/molehr\/5.7.656","article-title":"Secretory leukocyte protease inhibitor (SLPI) concentrations in cervical mucus of women with normal menstrual cycle.","volume":"5","author":"Moriyama","year":"1999","journal-title":"Mol Hum Reprod"},{"key":"2020071613393058000_R27","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1172\/JCI118926","article-title":"Constitutive and inducible expression of SKALP\/elafin provides anti-elastase defense in human epithelia.","volume":"98","author":"Pfundt","year":"1996","journal-title":"J Clin Invest"},{"key":"2020071613393058000_R28","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1159\/000058366","article-title":"Detection of the cervical gland area in threatened preterm labor using transvaginal sonography in the assessment of cervical maturation and the outcome of pregnancy.","volume":"53","author":"Yoshimatsu","year":"2002","journal-title":"Gynecol Obstet Invest"},{"key":"2020071613393058000_R29","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1056\/NEJMoa067815","article-title":"Progesterone and the risk of preterm birth among women with a short cervix.","volume":"357","author":"Fonseca","year":"2007","journal-title":"N Engl J Med"},{"key":"2020071613393058000_R30","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1002\/uog.5159","article-title":"Vaginal progesterone is associated with a decrease in risk for early preterm birth and improved neonatal outcome in women with a short cervix: a secondary analysis from a randomized, double-blind, placebo-controlled trial.","volume":"30","author":"DeFranco","year":"2007","journal-title":"Ultrasound Obstet Gynecol"},{"key":"2020071613393058000_R31","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1210\/endo-104-6-1745","article-title":"Stimulation of various 17 \u03b2- and 20 \u03b1-hydroxysteroid dehydrogenase activities by progestins in human endometrium.","volume":"104","author":"Tseng","year":"1979","journal-title":"Endocrinology"},{"key":"2020071613393058000_R32","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1172\/JCI117569","article-title":"17\u03b2-Hydroxysteroid dehydrogenase type 2: chromosomal assignment and progestin regulation of gene expression in human endometrium.","volume":"94","author":"Casey","year":"1994","journal-title":"J Clin Invest"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/93\/6\/2366\/9058295\/jcem2366.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jcem\/article-pdf\/93\/6\/2366\/9058295\/jcem2366.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,6]],"date-time":"2021-09-06T13:31:53Z","timestamp":1630935113000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/article\/93\/6\/2366\/2598936"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,6,1]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2008,6,1]]}},"URL":"https:\/\/doi.org\/10.1210\/jc.2007-2813","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,6,1]]}}}