{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T07:12:48Z","timestamp":1767856368424,"version":"3.49.0"},"reference-count":50,"publisher":"The Endocrine Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Stress induces CRH secretion that activates hypothalamic-pituitary-adrenal axis and is also abortogenic. In addition to hypothalamus, CRH and its analog urocortin (Ucn) are also secreted locally outside the brain where they activate mast cells leading to inflammation; however, the level of CRH and Ucn or mast cell mediators has not been examined in products of conception (POC). CRH and Ucn were measured by enzyme immunoassay, tryptase by fluoroenzyme immunoassay, and IL-8 by ELISA in POC of 7-9 wk gestation from Caucasian women; they were divided into group I with elective abortions (n = 4), group II with one spontaneous abortion (n = 12), and group III with at least two spontaneous abortions (n = 7). CRH, Ucn, tryptase, and IL-8 levels were higher (P &amp;lt; 0.05) in group III (8683 \u00b1 1201 pg\/g, 7961 \u00b1 1499 pg\/g, 1553 \u00b1 572 ng\/g, and 8317 \u00b1 1874 pg\/g, respectively) than group II (2561 \u00b1 314 pg\/g, 2349 \u00b1 394 pg\/g, 403 \u00b1 97 ng\/g, and 3199 \u00b1 449 pg\/g, respectively) and group I (163 \u00b1 162 pg\/g, 328 \u00b1 327 pg\/g, 72 \u00b1 31 ng\/g, and 3681 \u00b1 931 pg\/g, respectively). Immunostaining of POC showed significantly more tryptase in group III women. High POC levels of CRH and Ucn under stress in habitual spontaneous abortions may activate uterine mast cells to secrete abortogenic tryptase and IL-8.<\/jats:p>","DOI":"10.1210\/en.2003-0063","type":"journal-article","created":{"date-parts":[[2003,5,14]],"date-time":"2003-05-14T04:48:44Z","timestamp":1052887724000},"page":"2285-2290","source":"Crossref","is-referenced-by-count":46,"title":["High Levels of Intrauterine Corticotropin-Releasing Hormone, Urocortin, Tryptase, and Interleukin-8 in Spontaneous Abortions"],"prefix":"10.1210","volume":"144","author":[{"given":"Bhuvaneshwari","family":"Madhappan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics (B.M., D.K., S.C., W.B., T.C.T.), Tufts University School of Medicine, Boston, Massachusetts 02111;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duraisamy","family":"Kempuraj","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics (B.M., D.K., S.C., W.B., T.C.T.), Tufts University School of Medicine, Boston, Massachusetts 02111;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Spyridon","family":"Christodoulou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics (B.M., D.K., S.C., W.B., T.C.T.), Tufts University School of Medicine, Boston, Massachusetts 02111;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavros","family":"Tsapikidis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology (S.T.), InterBalkan Medical Center, Thessaloniki, 57001 Greece;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Boucher","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics (B.M., D.K., S.C., W.B., T.C.T.), Tufts University School of Medicine, Boston, Massachusetts 02111;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasilis","family":"Karagiannis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology (V.K.), Aristotle University School of Medicine, Thessaloniki, 54124 Greece;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Achilles","family":"Athanassiou","sequence":"additional","affiliation":[{"name":"Departments of Obstetrics and Gynecology (A.A.), Tufts-New England Medical Center, Boston, Massachusetts 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theoharis C.","family":"Theoharides","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics (B.M., D.K., S.C., W.B., T.C.T.), Tufts University School of Medicine, Boston, Massachusetts 02111;"},{"name":"Internal Medicine (T.C.T.), Tufts-New England Medical Center, Boston, Massachusetts 02111"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071618574988600_R1","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1093\/humrep\/16.7.1505","article-title":"Stress and immune mediators in miscarriage.","volume":"16","author":"Arck","year":"2001","journal-title":"Hum Reprod"},{"key":"2020071618574988600_R2","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1192\/bjp.167.6.799","article-title":"Life events and miscarriage.","volume":"167","author":"O\u2019Hare","year":"1995","journal-title":"Br J Psychiatry"},{"key":"2020071618574988600_R3","doi-asserted-by":"crossref","first-page":"S264","DOI":"10.1016\/S0002-9378(99)70713-1","article-title":"Stress-associated preterm delivery: the role of corticotropin-releasing hormone","volume":"180","author":"Lockwood","year":"1999","journal-title":"Am J Obstet Gynecol"},{"key":"2020071618574988600_R4","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1007\/BF03346896","article-title":"Human endometrium as a neuroendocrine tissue: expression, regulation and biological roles of endometrial corticotropin-releasing hormone (CRH) and opioid peptides.","volume":"20","author":"Zoumakis","year":"1997","journal-title":"J Endocrinol Invest"},{"key":"2020071618574988600_R5","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/S0002-9378(96)80024-X","article-title":"Circulating maternal corticotropin-releasing hormone and gonadotropin-releasing hormone in normal and abnormal pregnancies.","volume":"175","author":"Sorem","year":"1996","journal-title":"Am J Obstet Gynecol"},{"key":"2020071618574988600_R6","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1067\/mob.2002.121727","article-title":"The Preterm Prediction Study: the value of serum alkaline phosphatase, \u03b1-fetoprotein, plasma corticotropin-releasing hormone, and other serum markers for the prediction of spontaneous preterm birth.","volume":"186","author":"Moawad","year":"2002","journal-title":"Am J Obstet Gynecol"},{"key":"2020071618574988600_R7","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1067\/mob.2002.119635","article-title":"Maternal plasma corticotropin-releasing hormone trajectories vary depending on the cause of preterm delivery.","volume":"186","author":"McGrath","year":"2002","journal-title":"Am J Obstet Gynecol"},{"key":"2020071618574988600_R8","doi-asserted-by":"crossref","first-page":"R9","DOI":"10.1677\/joe.0.173r009","article-title":"Identification of urocortin mRNA and peptide in the human endometrium","volume":"173","author":"Florio","year":"2002","journal-title":"J Endocrinol"},{"key":"2020071618574988600_R9","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1053\/plac.2000.0570","article-title":"Localization and characterization of urocortin during human pregnancy.","volume":"21","author":"Clifton","year":"2000","journal-title":"Placenta"},{"key":"2020071618574988600_R10","first-page":"3807","article-title":"Human placenta and fetal membranes express human urocortin mRNA and peptide.","volume":"81","author":"Petraglia","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618574988600_R11","first-page":"618","article-title":"Characterization of urocortin in human pregnancy.","volume":"114","author":"Gu","year":"2001","journal-title":"Chin Med J"},{"key":"2020071618574988600_R12","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/j.1600-0897.1999.tb00073.x","article-title":"Decidual mast cells might be involved in the onset of human first-trimester abortion.","volume":"41","author":"Marx","year":"1999","journal-title":"Am J Reprod Immunol"},{"key":"2020071618574988600_R13","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1034\/j.1600-065X.2000.917305.x","article-title":"Mast cells in innate immunity.","volume":"173","author":"Mekori","year":"2000","journal-title":"Immunol Rev"},{"key":"2020071618574988600_R14","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1053\/ob.1996.v175.a74918","article-title":"Amniotic fluid embolism, anaphylaxis, and tryptase.","volume":"175","author":"Benson","year":"1996","journal-title":"Am J Obstet Gynecol"},{"key":"2020071618574988600_R15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0014-2999(97)83033-6","article-title":"Human mast cell tryptase: a stimulus of microvascular leakage and mast cell activation.","volume":"328","author":"He","year":"1997","journal-title":"Eur J Pharmacol"},{"key":"2020071618574988600_R16","first-page":"1201","article-title":"Interleukin-8 induces proliferation of endometrial stromal cells: a potential autocrine growth factor.","volume":"83","author":"Arici","year":"1998","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618574988600_R17","first-page":"1427","article-title":"Human decidua and in vitro decidualized endometrial stromal cells at term contain immunoreactive corticotropin-releasing factor (CRF) and CRF messenger ribonucleic acid.","volume":"74","author":"Petraglia","year":"1992","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618574988600_R18","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/0022-1759(92)90061-W","article-title":"Enzyme immunoassay techniques, an overview.","volume":"150","author":"Porstmann","year":"1992","journal-title":"J Immunol Methods"},{"key":"2020071618574988600_R19","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/BF01533368","article-title":"Development of a new, more sensitive immunoassay for human tryptase: use in systematic anaphylaxis.","volume":"14","author":"Schwartz","year":"1994","journal-title":"J Clin Immunol"},{"key":"2020071618574988600_R20","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1182\/blood.V93.10.3338.410k05_3338_3346","article-title":"Characterization of mast cell-committed progenitors present in human umbilical cord blood.","volume":"93","author":"Kempuraj","year":"1999","journal-title":"Blood"},{"key":"2020071618574988600_R21","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1016\/S0006-291X(87)80261-9","article-title":"The corticotropin releasing hormone gene is expressed in human placenta.","volume":"148","author":"Grino","year":"1987","journal-title":"Biochem Biophys Res Commun"},{"key":"2020071618574988600_R22","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/S1043-2760(98)00146-5","article-title":"Corticotropin-releasing hormone in human pregnancy and parturition.","volume":"10","author":"McLean","year":"1999","journal-title":"Trends Endocrinol Metab"},{"key":"2020071618574988600_R23","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/S0002-9378(98)70391-6","article-title":"Urocortin in pregnancy.","volume":"179","author":"Glynn","year":"1998","journal-title":"Am J Obstet Gynecol"},{"key":"2020071618574988600_R24","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1016\/S0002-9378(11)90606-1","article-title":"Premature elevation of maternal plasma CRH levels in pregnancies complicated by premature labor.","volume":"166","author":"Warren","year":"1992","journal-title":"Am J Obstet Gynecol"},{"key":"2020071618574988600_R25","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1111\/j.1471-0528.1995.tb09063.x","article-title":"Corticotropin-releasing hormone and corticotropin-releasing hormone binding protein in normal and preeclamptic human pregnancies.","volume":"102","author":"Perkins","year":"1995","journal-title":"Br J Obstet Gynaecol"},{"key":"2020071618574988600_R26","first-page":"1174","article-title":"Elevated levels of umbilical cord corticotropin releasing hormone in growth retarded fetuses.","volume":"77","author":"Goland","year":"1993","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618574988600_R27","doi-asserted-by":"crossref","first-page":"5706","DOI":"10.1210\/jcem.86.12.8080","article-title":"The utility of plasma CRH as a predictor of preterm delivery.","volume":"86","author":"Inder","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071618574988600_R28","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1210\/endo.139.1.5660","article-title":"Corticotropin-releasing hormone induces skin mast cell degranulation and increased vascular permeability, a possible explanation for its pro-inflammatory effects.","volume":"139","author":"Theoharides","year":"1998","journal-title":"Endocrinology"},{"key":"2020071618574988600_R29","first-page":"1349","article-title":"Potent mast cell degranulation and vascular permeability triggered by urocortin through activation of CRH receptors.","volume":"288","author":"Singh","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"2020071618574988600_R30","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/72247","article-title":"Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism.","volume":"6","author":"Steinhoff","year":"2000","journal-title":"Nat Med"},{"key":"2020071618574988600_R31","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/j.1464-410X.1995.tb07384.x","article-title":"Increased number of substance P positive nerve fibers in interstitial cystitis.","volume":"75","author":"Pang","year":"1995","journal-title":"Br J Urol"},{"key":"2020071618574988600_R32","first-page":"CR607","article-title":"T-helper (1) cytokines increase during early pregnancy in women with a history of recurrent spontaneous abortion","volume":"8","author":"Rezaei","year":"2002","journal-title":"Med Sci Monit"},{"key":"2020071618574988600_R33","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1111\/j.1600-0897.1997.tb00197.x","article-title":"Stress triggered abortions are associated with alterations of granulated cells into the decidua.","volume":"37","author":"Markert","year":"1997","journal-title":"Am J Reprod Immunol"},{"key":"2020071618574988600_R34","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0165-0378(02)00038-4","article-title":"Hormonal regulation of cytokine release by human fetal membranes at term gestation: effects of oxytocin, hydrocortisone and progesterone on tumour necrosis factor-\u03b1 and transforming growth factor-\u03b2 1 output.","volume":"56","author":"Zicari","year":"2002","journal-title":"J Reprod Immunol"},{"key":"2020071618574988600_R35","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S0301-2115(01)00289-5","article-title":"Detection of interleukin-6, interleukin-8, and interleukin-11 in plasma from women with spontaneous abortion.","volume":"98","author":"Koumantaki","year":"2001","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2020071618574988600_R36","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1093\/infdis\/165.5.957","article-title":"Interleukin-8 in cord sera: a sensitive and specific marker for the detection of preterm chorioamnionitis.","volume":"165","author":"Shimoya","year":"1992","journal-title":"J Infect Dis"},{"key":"2020071618574988600_R37","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1016\/S0022-5347(01)65247-9","article-title":"Stress-induced bladder mast cell activation: implications for interstitial cystitis.","volume":"157","author":"Spanos","year":"1997","journal-title":"J Urol"},{"key":"2020071618574988600_R38","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1097\/00004714-200204000-00001","article-title":"Mast cells and stress: a psychoneuroimmunological perspective.","volume":"22","author":"Theoharides","year":"2002","journal-title":"J Clin Psychopharmacol"},{"key":"2020071618574988600_R39","first-page":"A274","article-title":"Imaging neurogenic inflammation in patients with migraine headaches","volume":"52","author":"Papagallo","year":"1999","journal-title":"Neurology"},{"key":"2020071618574988600_R40","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1037\/0278-6133.19.6.510","article-title":"Life event stress and the association with spontaneous abortion in gravid women at an urban emergency department.","volume":"19","author":"Boyles","year":"2000","journal-title":"Health Psychol"},{"key":"2020071618574988600_R41","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0020-7292(00)00344-1","article-title":"Psychological stress and spontaneous abortion.","volume":"73","author":"Bashour","year":"2001","journal-title":"Int J Gynaecol Obstet"},{"key":"2020071618574988600_R42","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/BF00848326","article-title":"The relation between stress and disease activity in rheumatoid arthritis.","volume":"15","author":"Thomason","year":"1992","journal-title":"J Behav Med"},{"key":"2020071618574988600_R43","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1507\/endocrj.43.241","article-title":"Differential changes of corticotropin releasing hormone (CRH) concentrations in plasma and synovial fluids of patients with rheumatoid arthritis (RA).","volume":"43","author":"Nishioka","year":"1996","journal-title":"Endocr J"},{"key":"2020071618574988600_R44","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1172\/JCI116150","article-title":"Local secretion of corticotropin-releasing hormone in the joints of Lewis rats with inflammatory arthritis.","volume":"90","author":"Crofford","year":"1992","journal-title":"J Clin Invest"},{"key":"2020071618574988600_R45","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1159\/000069516","article-title":"Acute stress results in skin corticotropin-releasing hormone secretion, mast cell activation and vascular permeability, an effect mimicked by intradermal corticotropin-releasing hormone and inhibited by histamine-1 receptor antagonists.","volume":"130","author":"Lytinas","year":"2003","journal-title":"Int Arch Allergy Immunol"},{"key":"2020071618574988600_R46","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1093\/rheumatology\/35.2.120","article-title":"Elevated levels of corticotrophin-releasing factor binding protein in the blood of patients suffering from arthritis and septicaemia and the presence of novel ligands in synovial fluid.","volume":"35","author":"Woods","year":"1996","journal-title":"Br J Rheumatol"},{"key":"2020071618574988600_R47","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1056\/NEJM199505183322008","article-title":"The hypothalamic-pituitary-adrenal axis and immune-mediated inflammation.","volume":"332","author":"Chrousos","year":"1995","journal-title":"N Engl J Med"},{"key":"2020071618574988600_R48","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1126\/science.1925600","article-title":"Autocrine or paracrine inflammatory actions of corticotropin-releasing hormone in vivo.","volume":"254","author":"Karalis","year":"1991","journal-title":"Science"},{"key":"2020071618574988600_R49","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0165-5728(96)00178-6","article-title":"CRH and the immune system.","volume":"72","author":"Karalis","year":"1997","journal-title":"J Neuroimmunol"},{"key":"2020071618574988600_R50","volume-title":"Human mast cells synthesize and secrete corticotropin-releasing hormone (CRH) and urocortin (Ucn)","author":"Kempuraj","year":"2003"}],"container-title":["Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/144\/6\/2285\/9297811\/endo2285.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/endo\/article-pdf\/144\/6\/2285\/9297811\/endo2285.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T04:08:58Z","timestamp":1594958938000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/endo\/article\/144\/6\/2285\/2880764"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,6,1]]},"references-count":50,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2003,6,1]]}},"URL":"https:\/\/doi.org\/10.1210\/en.2003-0063","relation":{},"ISSN":["0013-7227","1945-7170"],"issn-type":[{"value":"0013-7227","type":"print"},{"value":"1945-7170","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,6,1]]}}}