help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
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
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kang, S. K.
Right arrow Articles by Leung, P. C. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kang, S. K.
Right arrow Articles by Leung, P. C. K.
Endocrinology Vol. 142, No. 2 671-679
Copyright © 2001 by The Endocrine Society

ARTICLES

Stimulation of Mitogen-Activated Protein Kinase by Gonadotropin-Releasing Hormone in Human Granulosa-Luteal Cells1

Sung Keun Kang2, Chen-Jei Tai, Parimal S. Nathwani, Kyung-Chul Choi and Peter C. K. Leung3

Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, British Columbia, Canada V6H 3V5

Address all correspondence and requests for reprints to: Peter C. K. Leung, Ph.D., Department of Obstetrics and Gynecology, University of British Columbia, 2H-30, 4490 Oak Street, Vancouver, British Columbia, Canada V6H 3V5. E-mail: peleung{at}interchange.ubc.ca

The present study investigated the activation of mitogen-activated protein kinases (MAPKs) by a GnRH agonist (GnRHa) in human granulosa-luteal cells (hGLCs). The phosphorylation state of p44 and p42 MAPK was examined using antibodies that distinguish phospho-p44/42 MAPK (Thr202/Tyr204) from total p44/42 MAPK (activated plus inactivated). Activation of MAPK by GnRHa was observed within 5 min and was sustained for 60 min after treatment. GnRHa stimulated MAPK activation in a dose-dependent manner, with maximum stimulation (6.7-fold over basal levels) at 10-7 M. Pretreatment with a protein kinase C (PKC) inhibitor, GF109203X, completely blocked GnRHa-induced MAPK activation. In addition, pretreatment with a PKC activator, phorbol-12-myristate 13-acetate, potentiated GnRH-induced MAPK activation. These results indicate that GnRHa stimulates MAPK activation through a PKC-dependent pathway in hGLCs, possibly coupled to Gq{alpha} protein. MAPK activation was also observed in response to 8-bromo-cAMP or cholera toxin, but not pertussis toxin. Forskolin (50 µM) substantially stimulated a rapid cAMP accumulation, whereas GnRHa (10-7 M) or pertussis toxin (100 mg/ml) did not affect basal intracellular cAMP levels. Cotreatment of GnRHa (10-7 M) did not attenuate forskolin- or hCG-stimulated cAMP accumulation. These results suggest that the GnRH receptor is probably not coupled to Gs{alpha} or Gi{alpha} in hGLCs. Finally, GnRHa (10-7 M) stimulated a significant increase in Elk-1 phosphorylation and c-fos messenger RNA expression, as revealed by an in vitro kinase assay and Northern blot analysis, respectively. These results clearly demonstrate that GnRH activates the MAPK cascade through a PKC-dependent pathway in the human ovary.




This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
J.-H. Choi, C. B. Gilks, N. Auersperg, and P. C. K. Leung
Immunolocalization of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Type I GnRH Receptor during Follicular Development in the Human Ovary
J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4562 - 4570.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
J.-H. Choi, K.-C. Choi, N. Auersperg, and P. C K Leung
Differential regulation of two forms of gonadotropin-releasing hormone messenger ribonucleic acid by gonadotropins in human immortalized ovarian surface epithelium and ovarian cancer cells.
Endocr. Relat. Cancer, June 1, 2006; 13(2): 641 - 651.
[Abstract] [Full Text] [PDF]

Home page
 Endocr Relat CancerHome page
K.-Y. Kim, K.-C. Choi, N. Auersperg, and P. C K Leung
Mechanism of gonadotropin-releasing hormone (GnRH)-I and -II-induced cell growth inhibition in ovarian cancer cells: role of the GnRH-I receptor and protein kinase C pathway.
Endocr. Relat. Cancer, March 1, 2006; 13(1): 211 - 220.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
Y. Kitajima, T. Endo, K. Nagasawa, K. Manase, H. Honnma, T. Baba, T. Hayashi, H. Chiba, N. Sawada, and T. Saito
Hyperstimulation and a Gonadotropin-Releasing Hormone Agonist Modulate Ovarian Vascular Permeability by Altering Expression of the Tight Junction Protein Claudin-5
Endocrinology, February 1, 2006; 147(2): 694 - 699.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
J. A. MacLean II, M. K. Rao, K. M.H. Doyle, J. S. Richards, and M. F. Wilkinson
Regulation of the Rhox5 Homeobox Gene in Primary Granulosa Cells: Preovulatory Expression and Dependence on SP1/SP3 and GABP
Biol Reprod, December 1, 2005; 73(6): 1126 - 1134.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
C.-M. Yeung, B.-S. An, C. K. Cheng, B. K.C. Chow, and P. C.K. Leung
Expression and transcriptional regulation of the GnRH receptor gene in human neuronal cells
Mol. Hum. Reprod., November 1, 2005; 11(11): 837 - 842.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
K. Tajima, K. Yoshii, S. Fukuda, M. Orisaka, K. Miyamoto, A. Amsterdam, and F. Kotsuji
Luteinizing Hormone-Induced Extracellular-Signal Regulated Kinase Activation Differently Modulates Progesterone and Androstenedione Production in Bovine Theca Cells
Endocrinology, July 1, 2005; 146(7): 2903 - 2910.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
C. K. Cheng and P. C. K. Leung
Molecular Biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Their Receptors in Humans
Endocr. Rev., April 1, 2005; 26(2): 283 - 306.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
B.-S. An, J.-H. Choi, K.-C. Choi, and P. C. K. Leung
Differential Role of Progesterone Receptor Isoforms in the Transcriptional Regulation of Human Gonadotropin-Releasing Hormone I (GnRH I) Receptor, GnRH I, and GnRH II
J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1106 - 1113.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
C.-J. Tai, S.-J. Chang, P. C. K. Leung, and C.-R. Tzeng
Adenosine 5'-Triphosphate Activates Nuclear Translocation of Mitogen-Activated Protein Kinases Leading to the Induction of Early Growth Response 1 and Raf Expression in Human Granulosa-Luteal Cells
J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 5189 - 5195.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. K. Cheng, B. K. C. Chow, and P. C. K. Leung
An Activator Protein 1-Like Motif Mediates 17{beta}-Estradiol Repression of Gonadotropin-Releasing Hormone Receptor Promoter via an Estrogen Receptor {alpha}-Dependent Mechanism in Ovarian and Breast Cancer Cells
Mol. Endocrinol., December 1, 2003; 17(12): 2613 - 2629.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
K. Tajima, A. Dantes, Z. Yao, K. Sorokina, F. Kotsuji, R. Seger, and A. Amsterdam
Down-Regulation of Steroidogenic Response to Gonadotropins in Human and Rat Preovulatory Granulosa Cells Involves Mitogen-Activated Protein Kinase Activation and Modulation of DAX-1 and Steroidogenic Factor-1
J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2288 - 2299.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. K. Cheng, C. M. Yeung, R. L. C. Hoo, B. K. C. Chow, and P. C. K. Leung
Oct-1 Is Involved in the Transcriptional Repression of the Gonadotropin-Releasing Hormone Receptor Gene
Endocrinology, December 1, 2002; 143(12): 4693 - 4701.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
J. Liu, T. Vanttinen, C. Hyden-Granskog, and R. Voutilainen
Regulation of follistatin-related gene (FLRG) expression by protein kinase C and prostaglandin E2 in cultured granulosa-luteal cells
Mol. Hum. Reprod., November 1, 2002; 8(11): 992 - 997.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
A.L. Johnson, E.V. Solovieva, and J.T. Bridgham
Relationship Between Steroidogenic Acute Regulatory Protein Expression and Progesterone Production in Hen Granulosa Cells During Follicle Development
Biol Reprod, October 1, 2002; 67(4): 1313 - 1320.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
C. K. Cheng, C. M. Yeung, B. K. C. Chow, and P. C. K. Leung
Characterization of a New Upstream GnRH Receptor Promoter in Human Ovarian Granulosa-Luteal Cells
Mol. Endocrinol., July 1, 2002; 16(7): 1552 - 1564.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. A. Dewi, D. R. E. Abayasekara, and C. P. D. Wheeler-Jones
Requirement for ERK1/2 Activation in the Regulation of Progesterone Production in Human Granulosa-Lutein Cells Is Stimulus Specific
Endocrinology, March 1, 2002; 143(3): 877 - 888.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
D. Pati and H. R. Habibi
Involvement of Protein Kinase C and Arachidonic Acid Pathways in the Gonadotropin-Releasing Hormone Regulation of Oocyte Meiosis and Follicular Steroidogenesis in the Goldfish Ovary
Biol Reprod, March 1, 2002; 66(3): 813 - 822.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
W. R. Duan, M. Ito, Y. Park, E. T. Maizels, M. Hunzicker-Dunn, and J. L. Jameson
GnRH Regulates Early Growth Response Protein 1 Transcription Through Multiple Promoter Elements
Mol. Endocrinol., February 1, 2002; 16(2): 221 - 233.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. L. Gyles, C. J. Burns, B. J. Whitehouse, D. Sugden, P. J. Marsh, S. J. Persaud, and P. M. Jones
ERKs Regulate Cyclic AMP-induced Steroid Synthesis through Transcription of the Steroidogenic Acute Regulatory (StAR) Gene
J. Biol. Chem., September 7, 2001; 276(37): 34888 - 34895.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2001 by The Endocrine Society