This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Petraglia, F. Articles by Vale, W. Search for Related Content PubMed PubMed Citation Articles by Petraglia, F. Articles by Vale, W. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB PROSTAGLANDIN F2ALPHA

Urocortin Stimulates Placental Adrenocorticotropin and Prostaglandin Release and Myometrial Contractility in Vitro

Department of Surgical Sciences (F.P.), Chair of Obstetrics and Gynecology, University of Udine, 33100 Udine, Italy; Department of Reproductive Medicine and Child Development (P.F., S.L., A.R.G.), Section of Obstetrics and Gynecology, University of Pisa, 56100 Pisa, Italy; Department of Obstetrics and Gynecology (C.B., L.M.), University of Torino, 10024 Torino, Italy; Auxologic Institute (A.M.D.B.), University of Milano, Milano, Italy; Department of Surgery (C.T., E.P.), Section of Gynecological Endocrinology, University of Tor Vergata, 00133 Rome, Italy; and The Clayton Foundation Laboratories for Peptide Biology (W.V.), Salk Institute, La Jolla, California

Address all correspondence and requests for reprints to: Felice Petraglia, M.D., Department of Surgical Sciences, Chair of Obstetrics and Gynecology, University of Udine, Piazzale S. Maria della Misericordia, 33100 Udine, Italy. E-mail: felice.petraglia{at}dsc.uniud.it

Urocortin is a new member of the CRF family. Multiple biological effects for urocortin have been shown in rats and in some in vitro models, showing a modulatory role in hormonal and behavioral functions. Human placenta expresses urocortin, but no information is available on the possible local biological actions. The aim of the present study was to evaluate the effect of urocortin on placental ACTH and prostaglandin (PG) secretion, as well as on myometrial contractility.

Various in vitro models were used. For investigating the effect of urocortin on ACTH release, primary cultures of human trophoblast cells were used. Culture media, collected before and after 3 h exposure to different doses of urocortin and ACTH, were measured by RIA. Trophoblast tissue explants were incubated for 24 h in the presence of increasing doses of urocortin, and prostaglandin E2 (PGE2) levels were measured by RIA. Strips of myometrial tissue were incubated in an organ bath and connected to an isometric smooth-muscle transducer in the presence of urocortin, with or without prostaglandin F2 (PGF2). In all these experiments, the effect of astressin (a CRF receptor antagonist) on urocortin-induced actions and the effect of equimolar doses of CRF were evaluated.

A dose-related increase of trophoblast ACTH or PGE2 was induced by urocortin, whereas astressin inhibited urocortin-stimulated ACTH or PGE2 release. Equimolar doses of CRF showed a similar effect on both ACTH and PGE2. Urocortin increased PGF2-induced myometrial contractility, and this effect was completely abolished by the addition of astressin.

The present study showed that human urocortin stimulates placental secretion of ACTH and PGE2, and modulates myometrial contractility, suggesting a role for this peptide in placental and intrauterine CRF pathways.

This article has been cited by other articles:

				F. M. Severi, C. Boni, L. Bruni, C. Bocchi, R. A. Aguiar, F. M. Reis, and F. Petraglia The Increase of Blood Flow in the Fetal Middle Cerebral Artery Correlates With the Onset of Labor at Term Reproductive Sciences, July 1, 2008; 15(6): 584 - 590. [Abstract] [PDF]

				L. Gao, C. Lu, C. Xu, Y. Tao, B. Cong, and X. Ni Differential Regulation of Prostaglandin Production Mediated by Corticotropin-Releasing Hormone Receptor Type 1 and Type 2 in Cultured Human Placental Trophoblasts Endocrinology, June 1, 2008; 149(6): 2866 - 2876. [Abstract] [Full Text] [PDF]

				P. Florio, E. A. Linton, M. Torricelli, E. Faldini, F. M. Reis, A. Imperatore, G. Calonaci, E. Picciolini, and F. Petraglia Prediction of Preterm Delivery Based on Maternal Plasma Urocortin J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4734 - 4737. [Abstract] [Full Text] [PDF]

				P Florio, P J Lowry, C Benedetto, L Galleri, M Torricelli, A Giovannelli, R Battista, F M Reis, and F Petraglia Maternal plasma corticotropin-releasing factor (CRF) and CRF-binding protein (CRF-BP) levels in post-term pregnancy: effect of prostaglandin administration Eur. J. Endocrinol., September 1, 2007; 157(3): 279 - 284. [Abstract] [Full Text] [PDF]

				E. W. Hillhouse and D. K. Grammatopoulos The Molecular Mechanisms Underlying the Regulation of the Biological Activity of Corticotropin-Releasing Hormone Receptors: Implications for Physiology and Pathophysiology Endocr. Rev., May 1, 2006; 27(3): 260 - 286. [Abstract] [Full Text] [PDF]

				M. Torricelli, E. Ignacchiti, A. Giovannelli, A. Merola, E. Scarpetti, G. Calonaci, E. Picciolini, P. Florio, F. M Reis, E. A Linton, et al. Maternal plasma corticotrophin-releasing factor and urocortin levels in post-term pregnancies Eur. J. Endocrinol., February 1, 2006; 154(2): 281 - 285. [Abstract] [Full Text] [PDF]

				A. Belmonte, C. Ticconi, S. Dolci, M. Giorgi, A. Zicari, A. Lenzi, E. A. Jannini, and E. Piccione Regulation of Phosphodiesterase 5 Expression and Activity in Human Pregnant and Non-pregnant Myometrial Cells by Human Chorionic Gonadotropin Reproductive Sciences, December 1, 2005; 12(8): 570 - 577. [Abstract] [PDF]

				W. Li and J. R. G. Challis Corticotropin-Releasing Hormone and Urocortin Induce Secretion of Matrix Metalloproteinase-9 (MMP-9) without Change in Tissue Inhibitors of MMP-1 by Cultured Cells from Human Placenta and Fetal Membranes J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6569 - 6574. [Abstract] [Full Text] [PDF]

				J. R. Lindsay and L. K. Nieman The Hypothalamic-Pituitary-Adrenal Axis in Pregnancy: Challenges in Disease Detection and Treatment Endocr. Rev., October 1, 2005; 26(6): 775 - 799. [Abstract] [Full Text] [PDF]

				P. Florio, M. Torricelli, L. Galleri, G. De Falco, E. Leucci, G. Calonaci, E. Picciolini, G. Ambrosini, E. A. Linton, and F. Petraglia High Fetal Urocortin Levels at Term and Preterm Labor J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5361 - 5365. [Abstract] [Full Text] [PDF]

				P. Florio, G. Calonaci, F. M. Severi, M. Torricelli, C. Bocchi, G. Fiore, E. A. Linton, and F. Petraglia Reduced Maternal Plasma Urocortin Concentrations and Impaired Uterine Artery Blood Flow at Human Mid Pregnancy Reproductive Sciences, April 1, 2005; 12(3): 191 - 194. [Abstract] [PDF]

				F. H. Bloomfield, M. H. Oliver, P. Hawkins, A. C. Holloway, M. Campbell, P. D. Gluckman, J. E. Harding, and J. R. G. Challis Periconceptional Undernutrition in Sheep Accelerates Maturation of the Fetal Hypothalamic-Pituitary-Adrenal Axis in Late Gestation Endocrinology, September 1, 2004; 145(9): 4278 - 4285. [Abstract] [Full Text] [PDF]

				A. Chen, A. Blount, J. Vaughan, B. Brar, and W. Vale Urocortin II Gene Is Highly Expressed in Mouse Skin and Skeletal Muscle Tissues: Localization, Basal Expression in Corticotropin-Releasing Factor Receptor (CRFR) 1- and CRFR2-Null Mice, and Regulation by Glucocorticoids Endocrinology, May 1, 2004; 145(5): 2445 - 2457. [Abstract] [Full Text] [PDF]

				N. Papadopoulou, J. Chen, H. S. Randeva, M. A. Levine, E. W. Hillhouse, and D. K. Grammatopoulos Protein Kinase A-Induced Negative Regulation of the Corticotropin-Releasing Hormone R1{alpha} Receptor-Extracellularly Regulated Kinase Signal Transduction Pathway: The Critical Role of Ser301 for Signaling Switch and Selectivity Mol. Endocrinol., March 1, 2004; 18(3): 624 - 639. [Abstract] [Full Text] [PDF]

				E. Chatzaki, I. Charalampopoulos, C. Leontidis, I. A. Mouzas, M. Tzardi, C. Tsatsanis, A. N. Margioris, and A. Gravanis Urocortin in Human Gastric Mucosa: Relationship to Inflammatory Activity J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 478 - 483. [Abstract] [Full Text] [PDF]

				P. Florio, L. Cobellis, J. Woodman, F. M. Severi, E. A. Linton, and F. Petraglia Levels of Maternal Plasma Corticotropin-Releasing Factor and Urocortin During Labor Reproductive Sciences, July 1, 2002; 9(4): 233 - 237. [Abstract] [PDF]

				D. K. Grammatopoulos, H. S. Randeva, M. A. Levine, E. S. Katsanou, and E. W. Hillhouse Urocortin, but Not Corticotropin-Releasing Hormone (CRH), Activates the Mitogen-Activated Protein Kinase Signal Transduction Pathway in Human Pregnant Myometrium: An Effect Mediated via R1{{alpha}} and R2{beta} CRH Receptor Subtypes and Stimulation of Gq-Proteins Mol. Endocrinol., December 1, 2000; 14(12): 2076 - 2091. [Abstract] [Full Text]

				E. Karteris, D. Grammatopoulos, H. Randeva, and E. W. Hillhouse Signal Transduction Characteristics of the Corticotropin-Releasing Hormone Receptors in the Feto-Placental Unit J. Clin. Endocrinol. Metab., May 1, 2000; 85(5): 1989 - 1996. [Abstract] [Full Text]

				A. Slominski, B. Roloff, J. Curry, M. Dahiya, A. Szczesniewski, and J. Wortsman The Skin Produces Urocortin J. Clin. Endocrinol. Metab., February 1, 2000; 85(2): 815 - 823. [Abstract] [Full Text]

				A. Chakravorty, S. Mesiano, and R. B. Jaffe Corticotropin-Releasing Hormone Stimulates P450 17{alpha}-Hydroxylase/17,20-Lyase in Human Fetal Adrenal Cells via Protein Kinase C J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3732 - 3738. [Abstract] [Full Text] [PDF]

				F. M. Reis, M. Fadalti, P. Florio, and F. Petraglia Putative Role of Placental Corticotropin-Releasing Factor in the Mechanisms of Human Parturition Reproductive Sciences, May 1, 1999; 6(3): 109 - 119. [Abstract] [PDF]