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 Garrel, G.
Right arrow Articles by Counis, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Garrel, G.
Right arrow Articles by Counis, R.
Endocrinology Vol. 139, No. 4 2163-2170
Copyright © 1998 by The Endocrine Society

ARTICLES

Evidence That Gonadotropin-Releasing Hormone Stimulates Gene Expression and Levels of Active Nitric Oxide Synthase Type I in Pituitary Gonadotrophs, a Process Altered by Desensitization and, Indirectly, by Gonadal Steroids1

Ghislaine Garrel2, Yannick Lerrant, Céline Siriostis, Annette Bérault, Solange Magre, Claude Bouchaud and Raymond Counis

Endocrinologie Cellulaire et Moléculaire de la Reproduction (G.G., Y.L., C.S., A.B., R.C.), Université Pierre & Marie Curie, CNRS-URA 1449, Paris, France; Université Française du Pacifique, Tahiti (Y.L.); Différenciation de la Gonade (S.M.), Université Pierre & Marie Curie, CNRS-URA 1449, Paris, France; and Institut des Neurosciences (C.B.), Université Pierre & Marie Curie, CNRS-URA 1488, Paris, France

Address all correspondence and requests for reprints to: Dr. Raymond Counis, Endocrinologie cellulaire et Moléculaire de la Reproduction, Université Pierre et Marie Curie, URA CNRS 1449, Case 244, 75252 Paris cedex 05, France. E-mail: Raymond.counis{at}snv.jussieu.fr

To determine the site and mechanism of action of gonadal steroids on pituitary nitric oxide synthase type I (NOS I), present in both gonadotrophs and folliculo-stellate cells, the effects of castration and steroids were examined in male rats, in the presence of a GnRH antagonist (Antarelix). Western analysis showed a rapid and substantial increase with time, after orchidectomy, of NOS I protein, the concentration doubling in 24 h and reaching a maximal 4- to 5-fold increase after 3–7 days, followed by a progressive decline after 2 weeks. Testosterone or estradiol replacement, or administration of GnRH antagonist, totally abolished the effects of castration, demonstrating a mediation of the steroid effects via GnRH. In noncastrated rats, steroids and the GnRH antagonist also caused a reduction in the levels of NOS I (by 50–60%), consistent with inhibition of endogenous GnRH stimulation. In marked contrast, administration of a potent GnRH agonist (Triptorelin) to intact rats increased the levels of NOS I. A time-course study with a long-lasting formulation showed that rise in NOS I developed rapidly after a lag of approximately 5 h, with a 2-fold increase detectable after 8 h and a maximal 4.5-fold after 48 h. The level declined afterwards in a manner consistent with homologous desensitization that may occur in the continuous presence of GnRH; however, the profile was different and delayed compared with those of gonadotropin release. As observed for NOS I protein, NOS I messenger RNA concentration was increased by castration or GnRH agonist and reduced by steroids or GnRH antagonist. Taken together, these data demonstrate that steroids indirectly regulate NOS I messenger RNA and protein levels, through the hypothalamic modulation of GnRH, which represents the primary regulator of NOS I. No effect of steroids on NOS I was seen in the posterior lobe. NADPH-diaphorase histochemistry coupled to immuno-identification of the cells revealed that the treatments affecting the concentration of NOS I concomitantly altered the activity but exclusively in gonadotrophs and not in folliculo-stellate cells (which do not respond to GnRH), reinforcing the idea that GnRH played a major regulatory role. Expression in gonadotrophs of a GnRH-dependent NOS I and the ensuing production of nitric oxide represents a potentially novel signaling pathway for the neuropeptide in the anterior pituitary, consistent with the previously reported GnRH-induced cGMP production, the role of which remains to be evaluated.




This article has been cited by other articles:


Home page
 EndocrinologyHome page
S. Lariviere, G. Garrel-Lazayres, V. Simon, N. Shintani, A. Baba, R. Counis, and J. Cohen-Tannoudji
Gonadotropin-Releasing Hormone Inhibits Pituitary Adenylyl Cyclase-Activating Polypeptide Coupling to 3',5'-Cyclic Adenosine-5'-Monophosphate Pathway in L{beta}T2 Gonadotrope Cells through Novel Protein Kinase C Isoforms and Phosphorylation of Pituitary Adenylyl Cyclase-Activating Polypeptide Type I Receptor
Endocrinology, December 1, 2008; 149(12): 6389 - 6398.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
F. Shafiee-Kermani, S.-o. Han, and W. L. Miller
Chronic Gonadotropin-Releasing Hormone Inhibits Activin Induction of the Ovine Follicle-Stimulating Hormone {beta}-Subunit: Involvement of 3',5'-Cyclic Adenosine Monophosphate Response Element Binding Protein and Nitric Oxide Synthase Type I
Endocrinology, July 1, 2007; 148(7): 3346 - 3355.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. Lariviere, G. Garrel, V. Simon, J.-W. Soh, J.-N. Laverriere, R. Counis, and J. Cohen-Tannoudji
Gonadotropin-Releasing Hormone Couples to 3',5'-Cyclic Adenosine-5'-Monophosphate Pathway through Novel Protein Kinase C{delta} and -{epsilon} in L{beta}T2 Gonadotrope Cells
Endocrinology, March 1, 2007; 148(3): 1099 - 1107.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. P. Cabilla, M. d. C. Diaz, L. I. Machiavelli, A. H. Poliandri, F. A. Quinteros, M. Lasaga, and B. H. Duvilanski
17{beta}-Estradiol Modifies Nitric Oxide-Sensitive Guanylyl Cyclase Expression and Down-Regulates Its Activity in Rat Anterior Pituitary Gland
Endocrinology, September 1, 2006; 147(9): 4311 - 4318.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
G. Galmiche, N. Richard, S. Corvaisier, and M.-L. Kottler
The Expression of Aromatase in Gonadotropes Is Regulated by Estradiol and Gonadotropin-Releasing Hormone in a Manner that Differs from the Regulation of Luteinizing Hormone
Endocrinology, September 1, 2006; 147(9): 4234 - 4244.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. A. Andric, T. S. Kostic, and S. S. Stojilkovic
Contribution of Multidrug Resistance Protein MRP5 in Control of Cyclic Guanosine 5'-Monophosphate Intracellular Signaling in Anterior Pituitary Cells
Endocrinology, July 1, 2006; 147(7): 3435 - 3445.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
A. Secondo, A. Pannaccione, M. Cataldi, R. Sirabella, L. Formisano, G. Di Renzo, and L. Annunziato
Nitric oxide induces [Ca2+]i oscillations in pituitary GH3 cells: involvement of IDR and ERG K+ currents
Am J Physiol Cell Physiol, January 1, 2006; 290(1): C233 - C243.
[Abstract] [Full Text] [PDF]

Home page
 ReproductionHome page
J. M Russell, E Murphree, J Janik, and P Callahan
Effect of steroids and nitric oxide on pituitary hormone release in ovariectomized, peripubertal rats
Reproduction, April 1, 2005; 129(4): 497 - 504.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. K. Bachir, G. Garrel, A. Lozach, J.-N. Laverriere, and R. Counis
The Rat Pituitary Promoter of the Neuronal Nitric Oxide Synthase Gene Contains an Sp1-, LIM Homeodomain-Dependent Enhancer and a Distinct Bipartite Gonadotropin-Releasing Hormone-Responsive Region
Endocrinology, September 1, 2003; 144(9): 3995 - 4007.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. A. Andric, A. E. Gonzalez-Iglesias, F. Van Goor, M. Tomic, and S. S. Stojilkovic
Nitric Oxide Inhibits Prolactin Secretion in Pituitary Cells Downstream of Voltage-Gated Calcium Influx
Endocrinology, July 1, 2003; 144(7): 2912 - 2921.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
X. Wei, M. Sasaki, H. Huang, V. L. Dawson, and T. M. Dawson
The Orphan Nuclear Receptor, Steroidogenic Factor 1, Regulates Neuronal Nitric Oxide Synthase Gene Expression in Pituitary Gonadotropes
Mol. Endocrinol., December 1, 2002; 16(12): 2828 - 2839.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. Garrel, A. Lozach, L. K. Bachir, J.-N. Laverriere, and R. Counis
Pituitary Adenylate Cyclase-activating Polypeptide Stimulates Nitric-oxide Synthase Type I Expression and Potentiates the cGMP Response to Gonadotropin-releasing Hormone of Rat Pituitary Gonadotrophs
J. Biol. Chem., November 22, 2002; 277(48): 46391 - 46401.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
T. S. Kostic, M. Tomic', S. A. Andric, and S. S. Stojilkovic
Calcium-independent and cAMP-dependent Modulation of Soluble Guanylyl Cyclase Activity by G Protein-coupled Receptors in Pituitary Cells
J. Biol. Chem., May 3, 2002; 277(19): 16412 - 16418.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
L. K. Bachir, J.-N. Laverriere, and R. Counis
Isolation and Characterization of a Rat Nitric Oxide Synthase Type I Gene Promoter that Confers Expression and Regulation in Pituitary Gonadotrope Cells
Endocrinology, November 1, 2001; 142(11): 4631 - 4642.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
T. S. Kostic, S. A. Andric, and S. S. Stojilkovic
Spontaneous and Receptor-Controlled Soluble Guanylyl Cyclase Activity in Anterior Pituitary Cells
Mol. Endocrinol., June 1, 2001; 15(6): 1010 - 1022.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
A. Gobbetti and M. Zerani
In Vitro Nitric Oxide Effects on Basal and Gonadotropin-Releasing Hormone-Induced Gonadotropin Secretion by Pituitary Gland of Male Crested Newt (Triturus carnifex) during the Annual Reproductive Cycle
Biol Reprod, May 1, 1999; 60(5): 1217 - 1223.
[Abstract] [Full Text]

Home page
 Endocr. Rev.Home page
J. J. Evans
Modulation of Gonadotropin Levels by Peptides Acting at the Anterior Pituitary Gland
Endocr. Rev., February 1, 1999; 20(1): 46 - 67.
[Abstract] [Full Text]


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 © 1998 by The Endocrine Society