Reduced expression of CRH receptor type 1 in upper segment human myometrium during labour
Open accessAbstract
Background: Corticotropin-releasing hormone (CRH) and CRH-related peptide are shown to modulate uterine contractility through two CRH receptor subtype, CRH-R1 and CRH-R2 during pregnancy. Through different signaling pathways, CRH-R1 maintains myometrial quiescence whereas CRH-R2 promotes smooth muscle contractility. We hypothesized that the expression of CRH receptors in myometrium might be changed during pregnancy and labour. Method: Immunohistochemistry, Western blot and RT-PCR were used to quantify the cellular localization, the protein levels and the mRNA variants of both CRH-R1 and CRH-R2 in upper segment (US) and lower segment (LS) myometrium from nonpregnant and pregnant women at term before or after labour. Results: CRH-R1 and CRH-R2 were predominately localized to myometrial smooth muscle cells in US and LS. The protein level of CRH-R1 in US was significantly down-regulated in pregnancy, with a further decrease at the onset of labour. However, the expression of CRH-R1 in LS remained unchanged during pregnancy and labour. No significant changes in CRH-R2 expression were observed in US or LS. Six variants of CRH-R1, CRH-R1alpha,-R1beta,-R1c, -R1e,-R1f and -R1g, were identified in nonpregnant and pregnant myometrium. CRH-R2alpha was identified in pregnant myometrium, whereas CRH-R2beta was identified in nonpregnant myometrium Conclusion: CRH-R1 and CRH-R2 are expressed in nonpregnant and pregnant US and LS myometrium. Changed expression of CRH receptors during labour may underlie the initiation of uterine contractility during parturition.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The direct actions of CRH on myometrial contractility involve distinct CRH receptor isoforms.
“The direct actions of CRH on myometrial contractility involve distinct CRH receptor isoforms.”
From Stress and the HPA Axis: Balancing Homeostasis and Fertility. (2017) · cites this paper as [64]
Expression of CRH-R1 decreases in the upper segment of the uterus during labor, which becomes highly contractile.
“However, expression of CRH-R1 decreases in the upper segment of the uterus during labor, which becomes highly contractile [64].”
From Stress and the HPA Axis: Balancing Homeostasis and Fertility. (2017) · cites this paper as [64]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Wadhwa, P. D., Porto, M., Garite, T. J., Chicz-DeMet, A., & Sandman, C. A. (1998) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(98)70219-4 · Cited by 251 · see citing works
Corticotropin releasing hormone and the skin
Slominski, A. (2006) · Frontiers in bioscience · doi:10.2741/1966 · Cited by 157 · see citing works
Flagged first, then by citations
Research works printed but not linked: 38
- McLean M Smith R Corticotrophin-releasing hormone and human parturition Reproduction 2001 121 493 501 11277868
- Hillhouse EW Grammatopoulos DK Role of stress peptides during human pregnancy and labour Reproduction 2002 124 323 329 12201805
- Challis J Matthews SG Gibb W Lye SJ Endocrine and paracrine regulation of birth at term and preterm Endocr Rev 2000 21 514 550 11041447
- Riley SC Challis JRG Corticotorphin-releasing hormone production by the placenta and fetal membranes Placenta 1991 12 105 119 1871070
- Sasaki A Shinkawa O Margioris AN Liotta AS Sato S Murakami D Go M Shimizu Y Hanew K Yoshinaga K Immunoreactive corticotropin-releasing hormone in human plasma during pregnancy, labor and delivery J Clin Endocrinol Metab 1987 64 224 229 3491832
- McLean M Bistis A Davies JJ Woods R Lowry PJ Smith R A placental clock controlling the length of human pregnancy Nat Med 1995 1 460 463 7585095
- Jones SA Challis JR Local stimulation of prostaglandin production by corticotropin-releasing hormone in human fetal membranes and placenta Biochem Biophys Res Commun 1989 159 192 199 2784314
- Jones SA Challis JR Effects of corticotropin-releasing hormone and adrenocorticotropin on prostaglandin output by human placenta and fetal membranes Gynecol Obstet Invest 1990 29 165 168 2162798
- Gao L Lu C Xu C Tao Y Cong B Ni X Differential Regulation of prostaglandin production mediated by corticotropin-releasing hormone receptor type 1 and type 2 in cultured human placental trophoblasts Endocrinology 2008 149 2866 76 18325997
- Yang R You X Tang X Gao L Ni X Corticotropin-releasing hormone inhibits progesterone production in cultured human placental trophoblasts J Mol Endocrinol 2006 37 533 540 17170093
- You X Yang R Tang X Gao L Ni X Corticotropin-releasing hormone stimulates estrogen biosynthesis in cultured human placental trophoblasts Biol Reprod 2006 74 1067 1072 16467490
- Linton EA Woodman JR Asboth G Glynn BP Plested CP Bernal AL Corticotrophin releasing hormone: its potential for a role in human myometrium Exp Physiol 2001 86 273 281 11429644
- Grammatopoulos DK The role of CRH receptors and their agonists in myometrial contractility and quiescence during pregnancy and labour Front Biosci 2007 12 561 571 17127317
- Suda T Kageyama K Sakihara S Nigawara T Physiological roles of urocortins, human homologues of fish urotensin I, and their receptors Peptides 2004 25 1689 701 15476936
- Petraglia F Florio P Gallo R Simoncini T Saviozzi M Di Blasio AM Vaughan J Vale W Human placenta and fetal membranes express human urocortin mRNA and peptide J Clin Endocrinol Metab 1996 81 3807 3810 8855842
- Imperatore A Florio P Torres PB Torricelli M Galleri L Toti P Occhini R Picciolini E Vale W Petraglia F Urocortin 2 and urocortin 3 are expressed by the human placenta, deciduas, and fetal membranes Am J Obstet Gynecol 2006 195 288 295 16626608
- Richard D Lin Q Timofeeva E The corticotropin-releasing factor family of peptides and CRF receptors: their roles in the regulation of energy balance Eur J Pharmacol 2002 440 189 197 12007535
- Hillhouse EW Grammatopoulos DK The molecular mechanisms underlying the regulation of the biological activity of corticotropin-releasing hormone receptors: implications for physiology and pathophysiology Endocr Rev 2006 27 260 286 16484629
- Pisarchik A Slominski A Molecular and functional characterization of novel CRFR1 isoforms from the skin Eur J Biochem 2004 271 2821 2830 15206947 PMC1201492
- Pisarchik A Slominski AT Alternative splicing of CRH-R1 receptors in human and mouse skin: identification of new variants and their differential expression FASEB J 2001 15 2754 2756 11606483
- Jin D He P You X Zhu X Dai L He Q Liu C Hui N Sha J Ni X Expression of corticotropin-releasing hormone receptor type 1 and type 2 in human pregnant myometrium Reprod Sci 2007 14 568 577 17959885
- Stevens MY Challis JRG Lye SJ Corticotropin-releasing hormone receptor subtype 1 is significantly up-regulated at the time of labor in the human myometrium J Clin Endocrinol Metab 1998 83 4107 4115 9814500
- Wetzka B Sehringer B Schäfer WR Hör C Benedek E Deppert WR Zahradnik HP Expression patterns of CRH, CRH receptors, and CRH binding protein in human gestational tissue at term Exp Clin Endocrinol Diabetes 2003 111 154 161 12784189
- Rodríguez-Liñares B Linton EA Phaneuf S Expression of corticotrophin-releasing hormone receptor mRNA and protein in the human myometrium J Endocrinol 1998 156 15 21 9496229
- Aggelidou E Hillhouse EW Grammatopoulos D Up-regulation of nitric oxide synthase and modulation of the guanylate cyclase activity by corticotrophin-releasing hormone but not urocortin II or urocortin III in cultured human pregnant myometrial cells Proc Natl Acad Sci USA 2002 99 3300 3305 11854458 PMC122513
- Karteris E Hillhouse EW Grammatopoulos D Urocortin II is expressed in human pregnant myometrial cells and regulates myosin light chain phosphorylation: potential role of the type-2 corticotropin-releasing hormone receptor in the control of myometrial contractility Endocrinology 2004 145 890 900 14592950
- Chomczynski P Sacchi N Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction Anal Biochem 1987 162 156 159 2440339
- Karteris E Papadopoulou N Grammatopoulos DK Hillhouse EW Expression and signalling characteristics of the corticotrophin-releasing hormone receptors during the implantation phase in the human endometrium J Mol Endocrinol 2004 32 21 32 14765990
- Rodríguez-Liñares B Phaneuf S López Bernal A Linton EA Levels of corticotrophin-releasing hormone receptor subtype 1 mRNA in pregnancy and during labour in human myometrium measured by quantitative competitive PCR J Mol Endocrinol 1998 21 201 208 9801463
- Hillhouse EW Grammatopoulos D Control of intracellular signalling by corticotropin-releasing hormone in human myometrium Front Horm Res 2001 27 66 74 11450436
- Grammatopoulos D Dai Y Chen J Karteris E apadopoulou N Easton AJ Hillhouse EW Human corticotripin-releasing hormone receptor: Difference in subtype expression between pregnant and nonpregnant myometria J Clin Endocrinol Metab 1998 83 2539 2544 9661640
- Grammatopoulos D Dai Y Randeva HS Levine MA Karteris E Easton AJ Hillhouse EW A novel spliced variant of the type 1 corticotropin-releasing hormone receptor with a deletion in the seventh transmembrane domain present in the human pregnant term myometrium and fetal membranes Mol Endocrinol 1999 13 2189 2202 10598591
- Markovic D Papadopoulou N Teli T Randeva H Levine MA Hillhouse EW Grammatopoulos DK Differential responses of corticotropin-releasing hormone receptor type 1 variants to protein kinase C phosphorylation J Pharmacol Exp Ther 2006 319 1032 1042 16956982
- Nabhan C Xiong Y Xie LY Abou-Samra AB The alternatively spliced type II corticotropin-releasing factor receptor, stably expressed in LLCPK-1 cells, is not well coupled to the G protein(s) Biochem Biophys Res Commun 1995 212 1015 1021 7626087
- Wille S Sydow S Palchaudhuri MR Spiess J Dautzenberg FM Identification of amino acids in the N-terminal domain of corticotropin-releasing factor receptor 1 that are important determinants of high-affinity ligand binding J Neurochem 1999 72 388 395 9886092
- Zmijewski MA Slominski AT RF1 receptor splicing in epidermal keratinocytes: potential biological role and environmental regulations J Cell Physiol 2009 218 C593 602 PMC2612097 19006179
- Markovic D Vatish M Gu M Slater D Newton R Lehnert H Grammatopoulos DK The onset of labor alters corticotropin-releasing hormone type 1 receptor variant expression in human myometrium: putative role of interleukin-1beta Endocrinology 2007 148 3205 3213 17431005
- Slominski A Zbytek B Pisarchik A Slominski RM Zmijewski MA Wortsman J CRH functions as a growth factor/cytokine in the skin J Cell Physiol 2006 206 780 791 16245303 PMC1351367
Cited by
Sorted by citations
Stress and the HPA Axis: Balancing Homeostasis and Fertility.
Joseph, D., & Whirledge, S. (2017) · International journal of molecular sciences · doi:10.3390/ijms18102224 · Cited by 290 · see citing works
- Authors
- Cong, B., Zhang, L., Gao, L., & Ni, X.
- Affiliations
- Second Military Medical University (CN)
- PLA Navy General Hospital (CN)
- Corresponding author
- Ni, Xin
- Venue
- Reproductive Biology and Endocrinology
- Published
- 2009-05-12
- Volume
- 7
- Issue
- 1
- Pages
- 43-43
- ISSN
- 1477-7827 (ISSN-L)
- PMC
- PMC2694199
- OpenAlex
- W2048022501
- Cited by
- 27
- References
- 2
- Citations by year
- 2025: 1 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 2 · 2017: 2 · 2015: 1 · 2014: 1 · 2013: 2 · 2012: 3
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Reproductive Biology and Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China
- People’s Liberation Army Navy General Hospital
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Obstetrics and Gynecology › Maternal and Perinatal Health Interventions
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy-related medical research
- Keywords
- corticotropin-releasing factor, CRH receptor type 1, myometrium, labour, uterine contractility, myometrial quiescence, pregnancy, term pregnancy, smooth muscle cells
- MeSH terms
- CRF Receptor, Type 1, Female, Humans, Immunohistochemistry, Labor, Obstetric, Myometrium, Pregnancy, RNA, Messenger, Uterine Contraction, Blotting, Western, Signal Transduction, Gene Expression, Alternative Splicing, Receptors, Corticotropin-Releasing Hormone
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review