This Article Full Text Full Text (PDF) Alert me when this article is cited 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 Prevot, V. Articles by Beauvillain, J.-C. Search for Related Content PubMed PubMed Citation Articles by Prevot, V. Articles by Beauvillain, J.-C.

Estradiol Coupling to Endothelial Nitric Oxide Stimulates Gonadotropin-Releasing Hormone Release from Rat Median Eminence Via a Membrane Receptor¹

INSERM, U-422, Unité de Neuroendocrinologie et Physiopathologie Neuronale (V.P., D.C., P.P., J.-C.B.), 59045 Lille Cedex, France; Neuroscience Research Institute, State University of New York (C.M.R., G.L.F., G.B.S.), Old Westbury, New York 11568; and the Division of Psychiatry, Harvard Medical School, Brigham and Women’s Hospital (G.L.F., G.B.S.), Boston, Massachusetts 02115

Address all correspondence and requests for reprints to: Dr. Vincent Prevot, INSERM, U-422, Unité de Neuroendocrinologie et Physiopathologie Neuronale, place de Verdun, 59045 Lille Cedex, France. E-mail: prevot{at}biserte.lille.inserm.fr

The median eminence (ME), which is the common termination field for adenohypophysiotropic systems, has been shown to produce nitric oxide (NO), a signaling molecule involved in neuroendocrine secretion. Using an ex vivo technique, 17ß-estradiol exposure to ME fragments, including vascular tissues, stimulated NO release within seconds in a concentration-dependent manner, whereas 17-estradiol or testosterone had no effect. 17ß-Estradiol conjugated to BSA (E₂-BSA) also stimulated NO release, suggesting mediation by a membrane surface receptor. Tamoxifen, an estrogen receptor inhibitor, antagonized the action of both 17ß-estradiol and E₂-BSA. Furthermore, estradiol-stimulated NO stimulates GnRH release. This was demonstrated by hemoglobin (a NO scavenger), N-nitro-L-arginine methyl ester, and L-N⁵-(1-iminoethyl)ornithine (nitric oxide synthase inhibitors) inhibition of estradiol stimulated NO and GnRH release. In this regard, L-N⁵-(1-iminoethyl)ornithine, specific for endotheliol constitutive nitric oxide synthase, was significantly more potent, suggesting that the estradiol-stimulated NO release arose from vascular endothelial cells. Additionally, the NO-stimulated GnRH release occurs via guanylyl cyclase activation in GnRH nerve terminals, as ODQ, a potent and selective inhibitor of NO-sensitive guanylyl cyclase, abolished the estradiol-stimulated GnRH release. The results suggest that at physiological concentrations, 17ß-estradiol may have immediate actions on ME endothelial cells via nongenomic signaling pathways leading to NO-stimulated GnRH release.

This article has been cited by other articles:

				A. E. Herbison Rapid actions of oestrogen on gonadotropin-releasing hormone neurons; from fantasy to physiology? J. Physiol., November 1, 2009; 587(21): 5025 - 5030. [Abstract] [Full Text] [PDF]

				X. d'Anglemont de Tassigny, C. Campagne, B. Dehouck, D. Leroy, G. R. Holstein, J.-C. Beauvillain, V. Buee-Scherrer, and V. Prevot Coupling of Neuronal Nitric Oxide Synthase to NMDA Receptors via Postsynaptic Density-95 Depends on Estrogen and Contributes to the Central Control of Adult Female Reproduction J. Neurosci., June 6, 2007; 27(23): 6103 - 6114. [Abstract] [Full Text] [PDF]

				S. Gingerich and T. L. Krukoff Estrogen Modulates Endothelial and Neuronal Nitric Oxide Synthase Expression via an Estrogen Receptor {beta}-Dependent Mechanism in Hypothalamic Slice Cultures Endocrinology, July 1, 2005; 146(7): 2933 - 2941. [Abstract] [Full Text] [PDF]

				J. A. Arreguin-Arevalo and T. M. Nett A Nongenomic Action of 17{beta}-Estradiol as the Mechanism Underlying the Acute Suppression of Secretion of Luteinizing Hormone Biol Reprod, July 1, 2005; 73(1): 115 - 122. [Abstract] [Full Text] [PDF]

				V. Matagne, M.-C. Lebrethon, A. Gerard, and J.-P. Bourguignon Kainate/Estrogen Receptor Involvement in Rapid Estradiol Effects in Vitro and Intracellular Signaling Pathways Endocrinology, May 1, 2005; 146(5): 2313 - 2323. [Abstract] [Full Text] [PDF]

				N. N. Bulayeva, A. L. Wozniak, L. L. Lash, and C. S. Watson Mechanisms of membrane estrogen receptor-{alpha}-mediated rapid stimulation of Ca2+ levels and prolactin release in a pituitary cell line Am J Physiol Endocrinol Metab, February 1, 2005; 288(2): E388 - E397. [Abstract] [Full Text] [PDF]

				S. De Seranno, C. Estrella, A. Loyens, A. Cornea, S. R. Ojeda, J.-C. Beauvillain, and V. Prevot Vascular Endothelial Cells Promote Acute Plasticity in Ependymoglial Cells of the Neuroendocrine Brain J. Neurosci., November 17, 2004; 24(46): 10353 - 10363. [Abstract] [Full Text] [PDF]

				S. Karanth, W. H. Yu, C. M. Mastronardi, and S. M. McCann 17{beta}-Estradiol Stimulates Ascorbic Acid and LHRH Release from the Medial Basal Hypothalamus in Adult Male Rats Experimental Biology and Medicine, October 1, 2004; 229(9): 926 - 934. [Abstract] [Full Text] [PDF]

				Y. Xia and T. L. Krukoff Estrogen Induces Nitric Oxide Production via Activation of Constitutive Nitric Oxide Synthases in Human Neuroblastoma Cells Endocrinology, October 1, 2004; 145(10): 4550 - 4557. [Abstract] [Full Text] [PDF]

				V. Matagne, G. Rasier, M.-C. Lebrethon, A. Gerard, and J.-P. Bourguignon Estradiol Stimulation of Pulsatile Gonadotropin-Releasing Hormone Secretion in Vitro: Correlation with Perinatal Exposure to Sex Steroids and Induction of Sexual Precocity in Vivo Endocrinology, June 1, 2004; 145(6): 2775 - 2783. [Abstract] [Full Text] [PDF]

				S. Bouret, S. De Seranno, J.-C. Beauvillain, and V. Prevot Transforming Growth Factor {beta}1 May Directly Influence Gonadotropin-Releasing Hormone Gene Expression in the Rat Hypothalamus Endocrinology, April 1, 2004; 145(4): 1794 - 1801. [Abstract] [Full Text] [PDF]

				C. E. Navarro, S. A. Saeed, C. Murdock, A. J. Martinez-Fuentes, K. K. Arora, L. Z. Krsmanovic, and K. J. Catt Erratum Mol. Endocrinol., December 1, 2003; 17(12): A - 2658. [Abstract] [Full Text] [PDF]

				C. E. Navarro, S. Abdul Saeed, C. Murdock, A. J. Martinez-Fuentes, K. K. Arora, L. Z. Krsmanovic, and K. J. Catt Regulation of Cyclic Adenosine 3',5'-Monophosphate Signaling and Pulsatile Neurosecretion by Gi-coupled Plasma Membrane Estrogen Receptors in Immortalized Gonadotropin-Releasing Hormone Neurons Mol. Endocrinol., September 1, 2003; 17(9): 1792 - 1804. [Abstract] [Full Text] [PDF]

				P. A. Orihuela, A. Parada-Bustamante, P. P. Cortes, C. Gatica, and H. B. Croxatto Estrogen Receptor, Cyclic Adenosine Monophosphate, and Protein Kinase A Are Involved in the Nongenomic Pathway by Which Estradiol Accelerates Oviductal Oocyte Transport in Cyclic Rats Biol Reprod, April 1, 2003; 68(4): 1225 - 1231. [Abstract] [Full Text] [PDF]

				T. Shakil, A. N. E. Hoque, M. Husain, and D. D. Belsham Differential Regulation of Gonadotropin-Releasing Hormone Secretion and Gene Expression by Androgen: Membrane Versus Nuclear Receptor Activation Mol. Endocrinol., November 1, 2002; 16(11): 2592 - 2602. [Abstract] [Full Text] [PDF]

				R. Gyurko, S. Leupen, and P. L. Huang Deletion of Exon 6 of the Neuronal Nitric Oxide Synthase Gene in Mice Results in Hypogonadism and Infertility Endocrinology, July 1, 2002; 143(7): 2767 - 2774. [Abstract] [Full Text] [PDF]

				H C Christian and J F Morris Rapid actions of 17{beta}-oestradiol on a subset of lactotrophs in the rat pituitary J. Physiol., March 1, 2002; 539(2): 557 - 566. [Abstract] [Full Text] [PDF]

				N. Ben-Jonathan and R. Hnasko Dopamine as a Prolactin (PRL) Inhibitor Endocr. Rev., December 1, 2001; 22(6): 724 - 763. [Abstract] [Full Text] [PDF]

				C. Knauf, S. Ferreira, M. Hamdane, C. Mailliot, V. Prevot, J.-C. Beauvillain, and D. Croix Variation of Endothelial Nitric Oxide Synthase Synthesis in the Median Eminence during the Rat Estrous Cycle: An Additional Argument for the Implication of Vascular Blood Vessel in the Control of GnRH Release Endocrinology, October 1, 2001; 142(10): 4288 - 4294. [Abstract] [Full Text] [PDF]

				S. Bouret, M. Tran Van Chuoi-Mariot, V. Prevot, D. Croix, T. Takumi, S. Jegou, H. Vaudry, J.-C. Beauvillain, and V. Mitchell Evidence that TGF{beta} May Directly Modulate POMC mRNA Expression in the Female Rat Arcuate Nucleus Endocrinology, September 1, 2001; 142(9): 4055 - 4065. [Abstract] [Full Text] [PDF]

				C. Knauf, V. Prevot, G. B. Stefano, G. Mortreux, J.-C. Beauvillain, and D. Croix Evidence for a Spontaneous Nitric Oxide Release from the Rat Median Eminence: Influence on Gonadotropin-Releasing Hormone Release Endocrinology, June 1, 2001; 142(6): 2343 - 2350. [Abstract] [Full Text] [PDF]

				R. Clarke, F. Leonessa, J. N. Welch, and T. C. Skaar Cellular and Molecular Pharmacology of Antiestrogen Action and Resistance Pharmacol. Rev., March 1, 2001; 53(1): 25 - 72. [Abstract] [Full Text] [PDF]

				J. Kamegai, H. Tamura, T. Shimizu, S. Ishii, H. Sugihara, and I. Wakabayashi Estrogen Receptor (ER){{alpha}}, But Not ER{beta}, Gene Is Expressed in Growth Hormone-Releasing Hormone Neurons of the Male Rat Hypothalamus Endocrinology, February 1, 2001; 142(2): 538 - 543. [Abstract] [Full Text] [PDF]

				L. Tseng, J. Mazella, M. S. Goligorsky, C. M. Rialas, and G. B. Stefano Dopamine and Morphine Stimulate Nitric Oxide Release in Human Endometrial Glandular Epithelial Cells Reproductive Sciences, November 1, 2000; 7(6): 343 - 347. [Abstract] [PDF]

				K. J. Suter, J.-P. Wuarin, B. N. Smith, F. E. Dudek, and S. M. Moenter Whole-Cell Recordings from Preoptic/Hypothalamic Slices Reveal Burst Firing in Gonadotropin-Releasing Hormone Neurons Identified with Green Fluorescent Protein in Transgenic Mice Endocrinology, October 1, 2000; 141(10): 3731 - 3736. [Abstract] [Full Text] [PDF]

				G. B. Stefano, P. Cadet, C. Breton, Y. Goumon, V. Prevot, J. P. Dessaint, J.-C. Beauvillain, A. S. Roumier, I. Welters, and M. Salzet Estradiol-stimulated nitric oxide release in human granulocytes is dependent on intracellular calcium transients: evidence of a cell surface estrogen receptor Blood, June 15, 2000; 95(12): 3951 - 3958. [Abstract] [Full Text] [PDF]

				A. B Ropero, E. Fuentes, J. M Rovira, C. Ripoll, B. Soria, and A. Nadal Non-genomic actions of 17{beta}-oestradiol in mouse pancreatic {beta}-cells are mediated by a cGMP-dependent protein kinase J. Physiol., December 1, 1999; 521(2): 397 - 407. [Abstract] [Full Text] [PDF]

				G. B. Stefano, V. Prevot, J.-C. Beauvillain, C. Fimiani, I. Welters, P. Cadet, C. Breton, J. Pestel, M. Salzet, and T. V. Bilfinger Estradiol Coupling to Human Monocyte Nitric Oxide Release Is Dependent on Intracellular Calcium Transients: Evidence for an Estrogen Surface Receptor J. Immunol., October 1, 1999; 163(7): 3758 - 3763. [Abstract] [Full Text] [PDF]

				H C Christian and J F Morris Rapid actions of 17{beta}-oestradiol on a subset of lactotrophs in the rat pituitary J. Physiol., March 1, 2002; 539(2): 557 - 566. [Abstract] [Full Text] [PDF]