AJP - Endo AJP: Heart and Circulatory Physiology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Endocrinol Metab (July 20, 2004). doi:10.1152/ajpendo.00200.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/5/E991    most recent
00200.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Luo, X.
Right arrow Articles by Chegini, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Luo, X.
Right arrow Articles by Chegini, N.
Submitted on May 6, 2004
Accepted on July 12, 2004

Gonadotropin Releasing Hormone and TGF-Beta Activate MAP Kinase and Differentially Regulate Fibronectin Expression in Endometrial Epithelial and Stromal Cells

Xiaoping Luo1, Li Ding1, and Nasser Chegini1*

1 Department of OB/GYN, University of Florida, Gainesville, FL, USA

* To whom correspondence should be addressed. E-mail: cheginin{at}obgyn.ufl.edu.

Gonadotropin releasing hormone analogue (GnRHa) is used for medical management of endometriosis and premature luteinizing hormone surge during controlled ovarian stimulation. Human endometrium expresses GnRH receptors and GnRHa alters the expression of transforming growth factor beta (TGF-{beta}) and receptors in endometrial cells. Since the diverse biological action of GnRHa and TGF-{beta} are mediated in part through mitogen-activated protein kinase (MAPK) pathway, we determined whether utilization of MAPK/ERK and transcriptional activation of immediate early genes, c-fos and c-jun, result in differential regulation of fibronectin, known as key regulator of embryo implantation and endometriosis progression. Using endometrial stromal cells (ESC) and endometrial epithelial cell line (HES) we demonstrated that GnRHa and TGF-{beta}1 in a dose-, time- and cell-dependent manner increased the level of phosphorylated ERK1/2 (pERK1/2). GnRH antagonist, antide also increased pERK1/2 induction in ESC and HES, while pretreatment reduced GnRHa-induced pERK2 in ESC, but not in HES. Co-treatments with GnRHa + TGF-{beta}1 did not have an additive or an inhibitory effect on pERK1/2 induction compared to GnRHa or TGF-{beta}1 action alone. TGF-{beta}1 and GnRHa increased ERK1/2 nuclear accumulation and inversely regulated the expression of c-fos and c-jun, and that of fibronectin in a cell specific manner. Pretreatment with U0126, a MEK1/2 inhibitor, blocked basal, as well as GnRHa- and TGF-{beta}1-induced pERK1/2, however it differentially affected c-fos, c-jun, and fibronectin expression. In conclusion, the results indicate that GnRHa and TGF-{beta} signaling through MAPK/ERK results in differential regulation of fibronectin expression in endometrial cells, a molecular mechanism where short- and long-term GnRHa therapy and locally expressed TGF-{beta} could influence embryo implantation and endometriosis implants, respectively.




This article has been cited by other articles:


Home page
 Mol Hum ReprodHome page
Q. Pan, X. Luo, T. Toloubeydokhti, and N. Chegini
The expression profile of micro-RNA in endometrium and endometriosis and the influence of ovarian steroids on their expression
Mol. Hum. Reprod., November 1, 2007; 13(11): 797 - 806.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
K. Kamiya, K. Sakakibara, E. J. Ryer, R. P. Hom, E. B. Leof, K. C. Kent, and B. Liu
Phosphorylation of the Cyclic AMP Response Element Binding Protein Mediates Transforming Growth Factor {beta}-Induced Downregulation of Cyclin A in Vascular Smooth Muscle Cells
Mol. Cell. Biol., May 1, 2007; 27(9): 3489 - 3498.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
N. Chegini, X. Luo, Q. Pan, A. Rhoton-Vlasak, and D.F. Archer
Endometrial expression of epithelial neutrophil-activating peptide-78 during the menstrual cycle or in progestin-only contraceptive users with breakthrough bleeding and the influence of doxycycline therapy
Hum. Reprod., February 1, 2007; 22(2): 427 - 433.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
L. W.T. Cheung, P. C.K. Leung, and A. S.T. Wong
Gonadotropin-Releasing Hormone Promotes Ovarian Cancer Cell Invasiveness through c-Jun NH2-Terminal Kinase-Mediated Activation of Matrix Metalloproteinase (MMP)-2 and MMP-9.
Cancer Res., November 15, 2006; 66(22): 10902 - 10910.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
R. Li, X. Luo, Q. Pan, I. Zineh, D. F. Archer, R.S. Williams, and N. Chegini
Doxycycline alters the expression of inflammatory and immune-related cytokines and chemokines in human endometrial cells: implication in irregular uterine bleeding
Hum. Reprod., October 1, 2006; 21(10): 2555 - 2563.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
J. M. Hastings, K. S. Jackson, P. A. Mavrogianis, and A. T. Fazleabas
The Estrogen Early Response Gene FOS Is Altered in a Baboon Model of Endometriosis
Biol Reprod, August 1, 2006; 75(2): 176 - 182.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 2004 by the American Physiological Society.