This Article Full Text Full Text (PDF) Submit a related Letter to the Editor 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 Jabbour, H. N. Articles by Boddy, S. C. Search for Related Content PubMed PubMed Citation Articles by Jabbour, H. N. Articles by Boddy, S. C.

Prostaglandin E₂ Induces Proliferation of Glandular Epithelial Cells of the Human Endometrium via Extracellular Regulated Kinase 1/2-Mediated Pathway

Medical Research Council Human Reproductive Sciences Unit, The University of Edinburgh Academic Centre, Edinburgh, Scotland EH16 4SB, United Kingdom

Address all correspondence and requests for reprints to: Dr. Henry N. Jabbour, Medical Research Council Human Reproductive Sciences Unit, The University of Edinburgh Academic Centre, Chancellor’s Building, 49 Little France Crescent, Edinburgh, Scotland EH16 4SB, United Kingdom. E-mail: h.jabbour{at}hrsu.mrc.ac.uk.

In this study, we investigated the effect of prostaglandin E₂ (PGE₂) on MAPK ERK1/2 protein phosphorylation and on proliferation of epithelial cells of the human endometrium. Treatment of proliferative phase endometrium with PGE₂ induced rapid phosphorylation of ERK1/2 proteins in glandular epithelial and endothelial cells. Treatment of human endometrial tissue with PGE₂ for 24 h resulted in increased incorporation of 5-bromo-2'-deoxyuridine (a marker of cellular proliferation) in glandular epithelial cells. To investigate further the effect of PGE₂ on proliferation of epithelial cells, we used an endometrial epithelial cell line (HES). HES cells express functional EP4 (with absence of expression of EP1, EP2, and EP3) receptors and stimulate cAMP release and rapid phosphorylation of ERK1/2 proteins in response to PGE₂ or forskolin. Treatment of HES cells with PGE₂ or forskolin alone resulted in a significant increase in HES cell proliferation compared with control untreated cells (P < 0.05). Cotreatment of the cells with PGE₂ or forskolin and PD98059 abolished the increase in cellular proliferation. These data demonstrate ERK1/2 phosphorylation in response to PGE₂ in the human endometrium and suggest that PGE₂ via EP4 receptor may induce glandular epithelial cell proliferation in ERK1/2- dependent manner during the proliferative phase of the menstrual cycle.

Abbreviations: BrdU, 5-Bromo-2'-deoxyuridine; COX, cyclooxygenase; EP1-EP4, four receptor subtypes for PGE₂; HES, endometrial epithelial cell line; PGE, prostaglandin E; PGH₂, prostaglandin H₂.

This article has been cited by other articles:

				I. Gashaw, S. Stiller, C. Boing, R. Kimmig, and E. Winterhager Premenstrual Regulation of the Pro-Angiogenic Factor CYR61 in Human Endometrium Endocrinology, May 1, 2008; 149(5): 2261 - 2269. [Abstract] [Full Text] [PDF]

				J. H. C. Kengni, I. St-Louis, S. Parent, V. Leblanc, C. Shooner, and E. Asselin Regulation of prostaglandin D synthase and prostacyclin synthase in the endometrium of cyclic, pregnant, and pseudopregnant rats and their regulation by sex steroids J. Endocrinol., November 1, 2007; 195(2): 301 - 311. [Abstract] [Full Text] [PDF]

				G. D. Stoner, H. Qin, T. Chen, P. S. Carlton, M. E. Rose, R. M. Aziz, and R. Dixit The effects of L-748706, a selective cyclooxygenase-2 inhibitor, on N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis Carcinogenesis, September 1, 2005; 26(9): 1590 - 1595. [Abstract] [Full Text] [PDF]

				C. Nicola, A. V. Timoshenko, S. J. Dixon, P. K. Lala, and C. Chakraborty EP1 Receptor-Mediated Migration of the First Trimester Human Extravillous Trophoblast: The Role of Intracellular Calcium and Calpain J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4736 - 4746. [Abstract] [Full Text] [PDF]

				M.L. Hull, A. Prentice, D.Y. Wang, R.P. Butt, S.C. Phillips, S.K. Smith, and D.S. Charnock-Jones Nimesulide, a COX-2 inhibitor, does not reduce lesion size or number in a nude mouse model of endometriosis Hum. Reprod., February 1, 2005; 20(2): 350 - 358. [Abstract] [Full Text] [PDF]

				S Battersby, H O D Critchley, A J de Brum-Fernandes, and H N Jabbour Temporal expression and signalling of prostacyclin receptor in the human endometrium across the menstrual cycle Reproduction, January 1, 2004; 127(1): 79 - 86. [Abstract] [Full Text] [PDF]