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 Lin, X.
Right arrow Articles by Conn, P. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lin, X.
Right arrow Articles by Conn, P. M.
Endocrinology Vol. 140, No. 1 358-364
Copyright © 1999 by The Endocrine Society

ARTICLES

Transcriptional Activation of Gonadotropin-Releasing Hormone (GnRH) Receptor Gene by GnRH: Involvement of Multiple Signal Transduction Pathways1

Xinwei Lin and P. Michael Conn

Oregon Regional Primate Research Center (X.L., P.M.C.), Beaverton, Oregon 97006; and the Department of Physiology and Pharmacology, Oregon Health Sciences University (P.M.C.), Portland, Oregon 97201

Address all correspondence and requests for reprints to: Dr. P. Michael Conn, Oregon Regional Primate Research Center, 505 NW 185th Avenue, Beaverton, Oregon 97006. E-mail: connm{at}ohsu.edu

Previous studies have shown that GnRH activates transcriptional activity of its own receptor (GnRHR) gene in part through the cAMP signal transduction pathway. In the present study we explored the possible involvement of multiple signal transduction pathways in GnRH regulation of GnRHR gene transcription; these studies relied upon a luciferase reporter gene vector (GnRHR-pXP2) containing a 1226-bp promoter fragment (-1164 to +62, relative to the major transcription start site) of the mouse GnRHR gene in GGH3 cells (GH3 cells stably expressing rat GnRHR). Activation of protein kinase C (PKC) by phorbol myristic acid significantly stimulated GnRHR-luciferase reporter gene (GnRHR-Luc) activity, but did not potentiate the stimulation of GnRHR-Luc activity by the GnRH agonist, buserelin (GnRH-A). Inhibition of PKC by PKC inhibitor (GF 109203X) or depletion of PKC blocked phorbol myristic acid- or GnRH-A-stimulated GnRHR-Luc activity, but did not affect (Bu)2cAMP-stimulated GnRHR-Luc activity. In addition, GnRH-A-stimulated GnRHR-Luc activity was inhibited by preventing external Ca2+ influx with the external Ca2+ chelator EGTA or the Ca2+ ion channel antagonist, D600. Surprisingly, overexpression of the mitogen-activated protein kinase (MAPK) kinase kinase (Raf-1) inhibited GnRHR-Luc activity and partially blocked GnRH-A-stimulated GnRHR-Luc activity. In contrast, inhibition of MAPK activity by MAPK kinase inhibitor (PD 98059) or by overexpression of kinase-deficient MAPKs activated basal and GnRH-A-stimulated GnRHR-Luc activity. These results suggested that PKC- and Ca2+-dependent signal transduction pathways participate in the GnRH activation of GnRHR promoter activity, and that the MAPK cascade is involved in the negative regulation of basal and GnRH-stimulated GnRHR transcriptional activity conferred by the 1226-bp promoter fragment.




This article has been cited by other articles:


Home page
 Biol. Reprod.Home page
H. B. Adewale, W. N. Jefferson, R. R. Newbold, and H. B. Patisaul
Neonatal Bisphenol-A Exposure Alters Rat Reproductive Development and Ovarian Morphology Without Impairing Activation of Gonadotropin-Releasing Hormone Neurons
Biol Reprod, October 1, 2009; 81(4): 690 - 699.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J.-P. Lai, S. Lai, F. Tuluc, M. F. Tansky, L. E. Kilpatrick, S. E. Leeman, and S. D. Douglas
Differences in the length of the carboxyl terminus mediate functional properties of neurokinin-1 receptor
PNAS, August 26, 2008; 105(34): 12605 - 12610.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
M. Liao, Y. Zhang, and M. L. Dufau
Protein Kinase C{alpha}-Induced Derepression of the Human Luteinizing Hormone Receptor Gene Transcription through ERK-Mediated Release of HDAC1/Sin3A Repressor Complex from Sp1 Sites
Mol. Endocrinol., June 1, 2008; 22(6): 1449 - 1463.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
D. J. Haisenleder, L. L. Burger, H. E. Walsh, J. Stevens, K. W. Aylor, M. A. Shupnik, and J. C. Marshall
Pulsatile Gonadotropin-Releasing Hormone Stimulation of Gonadotropin Subunit Transcription in Rat Pituitaries: Evidence for the Involvement of Jun N-Terminal Kinase But Not p38
Endocrinology, January 1, 2008; 149(1): 139 - 145.
[Abstract] [Full Text] [PDF]

Home page
 J Mol EndocrinolHome page
L L Burger, D J Haisenleder, A C Dalkin, and J C Marshall
Regulation of gonadotropin subunit gene transcription
J. Mol. Endocrinol., December 1, 2004; 33(3): 559 - 584.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
A. Ulloa-Aguirre, J. A. Janovick, A. Leanos-Miranda, and P. M. Conn
Misrouted cell surface GnRH receptors as a disease aetiology for congenital isolated hypogonadotrophic hypogonadism
Hum. Reprod. Update, March 1, 2004; 10(2): 177 - 192.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
R. G. Romanelli, T. Barni, M. Maggi, M. Luconi, P. Failli, A. Pezzatini, E. Pelo, F. Torricelli, C. Crescioli, P. Ferruzzi, et al.
Expression and Function of Gonadotropin-releasing Hormone (GnRH) Receptor in Human Olfactory GnRH-secreting Neurons: AN AUTOCRINE GnRH LOOP UNDERLIES NEURONAL MIGRATION
J. Biol. Chem., January 2, 2004; 279(1): 117 - 126.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. Sadie, G. Styger, and J. Hapgood
Expression of the Mouse Gonadotropin-Releasing Hormone Receptor Gene in {alpha}T3-1 Gonadotrope Cells Is Stimulated by Cyclic 3',5'-Adenosine Monophosphate and Protein Kinase A, and Is Modulated by Steroidogenic Factor-1 and Nur77
Endocrinology, May 1, 2003; 144(5): 1958 - 1971.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
G. Maya-Nunez and P. Michael Conn
Cyclic Adenosine 3',5'-Monophosphate (cAMP) and cAMP Responsive Element-Binding Protein Are Involved in the Transcriptional Regulation of Gonadotropin-Releasing Hormone (GnRH) Receptor by GnRH and Mitogen-Activated Protein Kinase Signal Transduction Pathway in GGH3 Cells
Biol Reprod, August 1, 2001; 65(2): 561 - 567.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
M. Baratta, L.A. West, A.M. Turzillo, and T.M. Nett
Activin Modulates Differential Effects of Estradiol on Synthesis and Secretion of Follicle-Stimulating Hormone in Ovine Pituitary Cells
Biol Reprod, February 1, 2001; 64(2): 714 - 719.
[Abstract] [Full Text]

Home page
 Mol Hum ReprodHome page
S. Wolfahrt, B. Kleine, H. Jarry, and W. G. Rossmanith
Endogenous regulation of the GnRH receptor by GnRH in the human placenta
Mol. Hum. Reprod., January 1, 2001; 7(1): 89 - 95.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Pincas, J.-N. Laverriere, and R. Counis
Pituitary Adenylate Cyclase-activating Polypeptide and Cyclic Adenosine 3',5'-Monophosphate Stimulate the Promoter Activity of the Rat Gonadotropin-releasing Hormone Receptor Gene via a Bipartite Response Element in Gonadotrope-derived Cells
J. Biol. Chem., June 22, 2001; 276(26): 23562 - 23571.
[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 © 1999 by The Endocrine Society