This Article Full Text Full Text (PDF) All Versions of this Article: 90/2/1028    most recent Author Manuscript (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 Okada, H. Articles by Salamonsen, L. A. Search for Related Content PubMed PubMed Citation Articles by Okada, H. Articles by Salamonsen, L. A. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB ESTRADIOL Related Collections Female Endocrinology

Requirement for Proprotein Convertase 5/6 during Decidualization of Human Endometrial Stromal Cells in Vitro

Prince Henry’s Institute of Medical Research, Clayton, Victoria 3168, Australia

Address all correspondence and requests for reprints to: Dr. Hidetaka Okada, Department of Obstetrics and Gynecology, Kansai Medical University, Moriguchi 570-8507, Japan. E-mail: hodaka{at}takii.kmu.ac.jp.

Decidualization of endometrial stromal cells (ESCs) is critical for embryo implantation and maintenance of pregnancy. Proprotein convertase (PC) 5/6 is suggested to play an important role in the processes of stromal cell decidualization and embryo implantation in the mouse. PC5/6 is a member of the PC family responsible for processing precursor proteins to their active forms by selective proteolysis. In this study, we investigated the regulation of PC5/6 mRNA and protein expression in human ESCs during decidualization in vitro. Real-time PCR analyses revealed a significant increase in PC5/6 mRNA levels in ESCs treated with 17ß-estradiol (E₂) plus medroxy-progesterone acetate during decidualization. On the other hand, E₂ alone did not increase PC5/6 mRNA expression. Intense PC5/6 immunoreactivity was observed in the cytoplasm of E₂ plus medroxy-progesterone acetate-treated ESCs (decidualized ESCs) compared with E₂-treated ESCs on d 12 of culture (nondecidualized ESCs). This PC5/6 immunoreactivity was abolished by cotreatment with ZK 98299, a progesterone receptor antagonist. Western blotting revealed PC5/6 as approximately 120-kDa bands (pro- and mature forms) and a 65-kDa band (C-terminally truncated form) in decidualized ESCs. Using an antisense morpholino approach, prolactin production, a typical marker for decidualization, was significantly attenuated in decidualized ESCs after treatment with PC5/6 morpholino antisense oligonucleotides in comparison with controls. These results suggest that PC5/6 plays a key role for decidualization in human endometrium.

This article has been cited by other articles:

				C Freyer, L M Kilpatrick, L A Salamonsen, and G Nie Pro-protein convertases (PCs) other than PC6 are not tightly regulated for implantation in the human endometrium Reproduction, June 1, 2007; 133(6): 1189 - 1197. [Abstract] [Full Text] [PDF]

				S. Tabibzadeh and A. Hemmati-Brivanlou Lefty at the Crossroads of "Stemness" and Differentiative Events Stem Cells, September 1, 2006; 24(9): 1998 - 2006. [Abstract] [Full Text] [PDF]

				E. Dimitriadis, C. Stoikos, Y.-L. Tan, and L. A. Salamonsen Interleukin 11 Signaling Components Signal Transducer and Activator of Transcription 3 (STAT3) and Suppressor of Cytokine Signaling 3 (SOCS3) Regulate Human Endometrial Stromal Cell Differentiation Endocrinology, August 1, 2006; 147(8): 3809 - 3817. [Abstract] [Full Text] [PDF]

				G. Nie, Y. Li, K. Hale, H. Okada, U. Manuelpillai, E. M. Wallace, and L. A. Salamonsen Serine Peptidase HTRA3 Is Closely Associated with Human Placental Development and Is Elevated in Pregnancy Serum Biol Reprod, February 1, 2006; 74(2): 366 - 374. [Abstract] [Full Text] [PDF]

				M. Tang, A. Mikhailik, I. Pauli, L. C. Giudice, A. T. Fazelabas, S. Tulac, D. D. Carson, D. G. Kaufman, C. Barbier, J. W. M. Creemers, et al. Decidual Differentiation of Stromal Cells Promotes Proprotein Convertase 5/6 Expression and Lefty Processing Endocrinology, December 1, 2005; 146(12): 5313 - 5320. [Abstract] [Full Text] [PDF]