{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2022,4,5]],"date-time":"2022-04-05T15:22:02Z","timestamp":1649172122013},"reference-count":52,"publisher":"The Endocrine Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1998,8,1]]},"abstract":"<jats:title>abstract<\/jats:title><jats:p>As term approaches, a number of key proteins [contraction-associated proteins (CAPs)] are expressed within the human myometrium that are essential for the activation of powerful coordinated contractions during labor. The nature of the signals that switch on the synthesis of CAPs in vivo is not known. The ryanodine-sensitive intracellular Ca2+ release channel (RyR2) is a CAP whose expression in vitro is activated by transforming growth factor-\u03b2 (TGF\u03b2). The present experiments were performed to determine whether TGF\u03b2 and TGF\u03b2 receptors are present in the human myometrium at term and to explore the idea that they might form part of a signaling system in vivo. TGF\u03b2 receptor types I and II, but not III, were demonstrated in myometrial smooth muscle in tissue taken from nonpregnant, pregnant nonlaboring, and spontaneous laboring women. Western blotting was used subsequently to determine the relative expression of TGF\u03b2 receptor types I and II. Using nonpregnant myometrium as a baseline control the levels of expression of receptor types I and II were significantly increased by 168 \u00b1 19% (n = 6) and 162 \u00b1 22% (n = 7) in pregnant nonlaboring myometrium. In spontaneous laboring myometrium the levels of TGF\u03b2 receptor type I and II expression were 93 \u00b1 12% (n = 6) and 85 \u00b1 11% (n = 7), respectively, compared to nonpregnant control values and were significantly lower than levels in pregnant nonlaboring tissues. The total TGF\u03b21 levels in the myometrial tissues were 334 \u00b1 10, 534 \u00b1 73, and 674 \u00b1 106 pg\/g tissue wet wt in nonpregnant, pregnant nonlaboring, and spontaneous laboring myometrium (n = 3 in each group), respectively. Thus, the TGF\u03b2 signaling system appears to be up-regulated in the myometrium before the onset of parturition. The apparent loss of receptors in the spontaneous laboring samples in the presence of elevated total levels of TGF\u03b2 may be indicative of agonist-induced receptor down-regulation. These observations support the idea that cytokines, in particular TGF\u03b21, may play a role in the normal processes that prepare the myometrium for parturition at term.<\/jats:p>","DOI":"10.1210\/jcem.83.8.4992","type":"journal-article","created":{"date-parts":[[2014,1,8]],"date-time":"2014-01-08T17:03:29Z","timestamp":1389200609000},"page":"2987-2992","source":"Crossref","is-referenced-by-count":1,"title":["Gestational Changes in the Levels of Transforming Growth Factor-\u03b21 (TGF\u03b21) and TGF\u03b2 Receptor Types I and II in the Human Myometrium1"],"prefix":"10.1210","volume":"83","author":[{"given":"Panadda","family":"Hatthachote","sequence":"first","affiliation":[{"name":"Departments of Surgical Sciences (J.I.G.) and Obstetrics and Gynecology, The Medical School, University of Newcastle upon Tyne, United Kingdom NE2 4HH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanna","family":"Morgan","sequence":"additional","affiliation":[{"name":"Departments of Surgical Sciences (J.I.G.) and Obstetrics and Gynecology, The Medical School, University of Newcastle upon Tyne, United Kingdom NE2 4HH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William","family":"Dunlop","sequence":"additional","affiliation":[{"name":"Departments of Surgical Sciences (J.I.G.) and Obstetrics and Gynecology, The Medical School, University of Newcastle upon Tyne, United Kingdom NE2 4HH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G. Nicholas","family":"Europe-Finner","sequence":"additional","affiliation":[{"name":"Departments of Surgical Sciences (J.I.G.) and Obstetrics and Gynecology, The Medical School, University of Newcastle upon Tyne, United Kingdom NE2 4HH"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James I.","family":"Gillespie","sequence":"additional","affiliation":[{"name":"Departments of Surgical Sciences (J.I.G.) and Obstetrics and Gynecology, The Medical School, University of Newcastle upon Tyne, United Kingdom NE2 4HH"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","reference":[{"key":"2020071613532286300_R1","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/0378-4320(96)01529-1","article-title":"Initiation of parturition.","volume":"42","year":"1996","journal-title":"Anim Reprod Sci"},{"key":"2020071613532286300_R2","author":"Lopez 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human chorion cells.","volume":"30","author":"Pollard","year":"1993","journal-title":"Am J Reprod Immunol"},{"key":"2020071613532286300_R22","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1016\/0002-9378(93)90420-N","article-title":"5-Hydroxyeicosatetraenoic acid biosynthesis by gestational tissues.","volume":"169","author":"Edwin","year":"1993","journal-title":"Am J Obstet Gynecol"},{"key":"2020071613532286300_R23","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1210\/endo.132.6.8504751","article-title":"Identification and expression of G-proteins in human myometrium: up-regulation of G\u03b1s in pregnancy.","volume":"132","author":"EuropeFinner","year":"1993","journal-title":"Endocrinology"},{"key":"2020071613532286300_R24","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye 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steroids.","volume":"130","author":"Das","year":"1992","journal-title":"Endocrinology"},{"key":"2020071613532286300_R36","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1210\/mend-4-7-965","article-title":"Cell type-specific expression of transforming growth factor-\u03b21 in the mouse uterus during the periimplantation period.","volume":"4","author":"Tamada","year":"1990","journal-title":"Mol Endocrinol"},{"key":"2020071613532286300_R37","doi-asserted-by":"crossref","first-page":"5707","DOI":"10.1016\/S0021-9258(18)60623-4","article-title":"Bovine adrenocortical cells exhibit high affinity transforming growth factor-beta receptors which are regulated by adrenocorticotropin.","volume":"263","author":"Cochet","year":"1988","journal-title":"J Biol Chem"},{"key":"2020071613532286300_R38","first-page":"107","article-title":"Expression and localization of transforming growth factor-beta receptors type I and type II in the rat ventral prostate during regression.","volume":"10","author":"Kim","year":"1996","journal-title":"Mol Endocrinol"},{"key":"2020071613532286300_R39","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/1043-4666(93)90027-3","article-title":"Elevation of amniotic fluid interleukin 6 (IL-6), IL-8 and granulocyte colony stimulating factor (G-CSF) in term and preterm parturition.","volume":"5","author":"Saito","year":"1993","journal-title":"Cytokine"},{"key":"2020071613532286300_R40","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/0029-7844(95)93704-4","article-title":"Interleukin-8 synthesis and the onset of labour.","volume":"86","author":"Osmers","year":"1995","journal-title":"Obstet Gynecol"},{"key":"2020071613532286300_R41","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/0960-0760(96)00016-7","article-title":"Progestin regulation of interleukin-8 mRNA levels and protein synthesis in human endometrial stromal cells.","volume":"58","author":"Arici","year":"1996","journal-title":"J Steroid Biochem Mol Biol"},{"key":"2020071613532286300_R42","first-page":"3004","article-title":"Modulation of the levels of interleukin-8 messenger ribonucleic acid and interleukin-8 protein synthesis in human endometrial stromal cells by transforming growth factor-\u03b21.","volume":"81","author":"Arici","year":"1996","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071613532286300_R43","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0014-5793(95)01462-4","article-title":"Dansyl cadaverine regulates ligand-induced endocytosis of interleukin-8 receptor in human polymorphonuclear neutrophils.","volume":"378","author":"Ray","year":"1996","journal-title":"FEBS Lett"},{"key":"2020071613532286300_R44","doi-asserted-by":"crossref","first-page":"R5","DOI":"10.1677\/joe.0.141R005","article-title":"Internalization of the type-I angiotensin-II receptor (AT1) and angiotensin II function in the rat adrenal zona glomerulosa cell","volume":"141","author":"Vinson","year":"1994","journal-title":"J Endocrinol."},{"key":"2020071613532286300_R45","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/sj.bjp.0700858","article-title":"Somatostatin receptors in neuro2A neuroblastoma cells: operational characteristics.","volume":"120","author":"Koenig","year":"1997","journal-title":"Br J Pharmacol"},{"key":"2020071613532286300_R46","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1124\/mol.52.1.105","article-title":"The mu-opioid receptor down-regulates differently from the delta opioid receptor: requirement of a high affinity receptor G protein complex formation.","volume":"52","author":"Chakrabarti","year":"1997","journal-title":"Mol Pharmacol"},{"key":"2020071613532286300_R47","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1016\/0002-9378(94)90415-4","article-title":"Receptors for and myometrial responses to oxytocin and vasopressin in preterm and term human 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