This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited 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 Iwase, A. Articles by Kikkawa, F. Search for Related Content PubMed PubMed Citation Articles by Iwase, A. Articles by Kikkawa, F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH

Neutral Endopeptidase Expressed by Decidualized Stromal Cells Suppresses Akt Phosphorylation and Deoxyribonucleic Acid Synthesis Induced by Endothelin-1 in Human Endometrium

Departments of Obstetrics and Gynecology (A.I., H.A., D.S., T.H., Y.S., M.G., F.K.) and Maternal and Perinatal Medicine (A.I., T.H.), Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; and Division of Pathology (T.N.), Clinical Laboratory, Nagoya University Hospital, Nagoya 466-8560, Japan

Address all correspondence and requests for reprints to: Dr. Akira Iwase, Department of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: akiwase{at}med.nagoya-u.ac.jp.

Endothelin-1 (ET-1) in human endometrium has been proposed to have a potential paracrine role, for its receptors are also present within this tissue. In addition, the expression of ET-1 varies during the menstrual cycle, and therefore, ET-1 may be involved in the cyclic change of the human endometrium, such as proliferation and decidualization. However, neither the inactivation of ET-1 in the endometrium nor the paracrine effect of ET-1 on endometrial cells has been determined. We investigated the production of ET-1 and the presence of neutral endopeptidase (NEP), which cleaves and inactivates ET-1, in primary cultured human endometrial cells. We found primary cultured endometrial epithelial cells, not stromal cells, to be the major source of ET-1. Western blot analysis and RT-PCR demonstrated that NEP was predominantly expressed by endometrial stromal cells. We also demonstrated that ET-1 stimulated the phosphorylation of Akt and DNA synthesis in endometrial stromal cells via the ET_A receptor and phospahtidylinositol-3 kinase signaling pathways. The effect of ET-1 was regulated by NEP expressed by stromal cells. We also found that conditioned medium containing ET-1 from endometrial epithelial cell culture stimulated phosphorylation of Akt via the ET_A receptor. In conclusion, ET-1 has a paracrine effect of Akt phosphorylation and cell proliferation on endometrial stromal cells, which occurs via the ET_A receptor and phospahtidylinositol-3 kinase signaling pathways, and is regulated by cell-surface NEP.

This article has been cited by other articles:

				O. Blanco, I. Tirado, R. Munoz-Fernandez, A. C. Abadia-Molina, J. M. Garcia-Pacheco, J. Pena, and E. G. Olivares Human decidual stromal cells express HLA-G Effects of cytokines and decidualization Hum. Reprod., January 1, 2008; 23(1): 144 - 152. [Abstract] [Full Text] [PDF]

				A. Iwase, H. Ando, T. Nagasaka, M. Goto, T. Harata, and F. Kikkawa Distribution of Endothelin-converting Enzyme-1 and Neutral Endopeptidase in Human Endometrium J. Histochem. Cytochem., December 1, 2007; 55(12): 1229 - 1235. [Abstract] [Full Text] [PDF]