help button home button Endocrine Society Molecular Endocrinology ENDO 08 Sessions Library
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
This version published online on September 26, 2002
Molecular Endocrinology, doi:10.1210/me.2002-0163
Molecular Endocrinology Vol. 0, No. 2002 200201631-
doi:10.1210/me.2002-0163
Copyright © 2002 by the Endocrine Society.
This Article
Right arrow Author Manuscript (PDF)
Right arrow All Versions of this Article:
16/12/2872    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
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
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 DeFazio, R. A.
Right arrow Articles by Moenter, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by DeFazio, R. A.
Right arrow Articles by Moenter, S. M.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*MUSCIMOL

Submitted on May 2, 2002
Accepted on September 9, 2002

ACTIVATION OF GABAA RECEPTORS EXCITES GnRH NEURONS

R. Anthony DeFazio1, Sabine Heger1, Sergio R. Ojeda1, and Suzanne M. Moenter1*

1 Departments of Internal Medicine and Cell Biology, and NSF Center for Biological Timing, University of Virginia, Charlottesville, VA 22908, Division of Neuroscience, Oregon National Primate Research Center, Beaverton, OR 97006

* To whom correspondence should be addressed. E-mail: smm4n{at}virginia.edu.

GABA, acting through GABAA receptors (GABAAR), is hypothesized to suppress reproduction by inhibiting GnRH secretion, but GABA actions directly on GnRH neurons are not well established. In GFP-identified adult mouse GnRH neurons in brain slices, gramicidin-perforated-patch-clamp experiments revealed the reversal potential (EGABA) for current through GABAARs was depolarized relative to the resting potential and that rapid GABA application elicited action potentials in GnRH neurons but not controls. The consequence of GABAAR activation depends on intracellular chloride levels, which are maintained by homeostatic mechanisms. Membrane proteins that typically extrude chloride (KCC-2 cotransporter, ClC-2 channel) were absent from the GT1-7 immortalized GnRH cell line and GnRH neurons in situ or were not localized to the proper cell compartment for function. In contrast, GT1-7 cells and some GnRH neurons expressed the chloride accumulating cotransporter NKCC-1. Patch-clamp experiments showed that blockade of NKCC hyperpolarized EGABA by lowering intracellular chloride. Regardless of reproductive state, rapid GABA application excited GnRH neurons. In contrast, bath application of the GABAAR agonist muscimol transiently increased then suppressed firing; suppression persisted 4-15 min. Rapid activation of GABAAR thus excites GnRH neurons whereas prolonged activation reduces excitability, suggesting the physiological consequence of synaptic activation of GABAAR in GnRH neurons is excitation.
Key words: GnRH • GABA • GABAA receptor • chloride • gramicidin • patch clamp




This article has been cited by other articles:


Home page
 Integr. Comp. Biol.Home page
C. B. Roberts and K. J. Suter
Emerging methodologies for the study of hypothalamic gonadotropin-releasing-hormone (GnRH) neurons
Integr. Comp. Biol., November 1, 2008; 48(5): 548 - 559.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. A. Christian and S. M. Moenter
Critical Roles for Fast Synaptic Transmission in Mediating Estradiol Negative and Positive Feedback in the Neural Control of Ovulation
Endocrinology, November 1, 2008; 149(11): 5500 - 5508.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. A. Christian, C. Glidewell-Kenney, J. L. Jameson, and S. M. Moenter
Classical Estrogen Receptor {alpha} Signaling Mediates Negative and Positive Feedback on Gonadotropin-Releasing Hormone Neuron Firing
Endocrinology, November 1, 2008; 149(11): 5328 - 5334.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. A. Christian and S. M. Moenter
Vasoactive Intestinal Polypeptide Can Excite Gonadotropin-Releasing Hormone Neurons in a Manner Dependent on Estradiol and Gated by Time of Day
Endocrinology, June 1, 2008; 149(6): 3130 - 3136.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. L. Bogusz, S. L. Hardy, M. N. Lehman, J. M. Connors, S. M. Hileman, J. H. Sliwowska, H. J. Billings, C. J. McManus, M. Valent, S. R. Singh, et al.
Evidence that {gamma}-Aminobutyric Acid Is Part of the Neural Circuit Mediating Estradiol Negative Feedback in Anestrous Ewes
Endocrinology, June 1, 2008; 149(6): 2762 - 2772.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
J. W. Hill, J. K. Elmquist, and C. F. Elias
Hypothalamic pathways linking energy balance and reproduction
Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E827 - E832.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
C. A. Christian and S. M. Moenter
Estradiol Induces Diurnal Shifts in GABA Transmission to Gonadotropin-Releasing Hormone Neurons to Provide a Neural Signal for Ovulation
J. Neurosci., February 21, 2007; 27(8): 1913 - 1921.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
E. C. Cottrell, R. E. Campbell, S.-K. Han, and A. E. Herbison
Postnatal Remodeling of Dendritic Structure and Spine Density in Gonadotropin-Releasing Hormone Neurons
Endocrinology, August 1, 2006; 147(8): 3652 - 3661.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
S.K. Blank, C.R. McCartney, and J.C. Marshall
The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome
Hum. Reprod. Update, July 1, 2006; 12(4): 351 - 361.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. El-Etr, Y. Akwa, E.-E. Baulieu, and M. Schumacher
The Neuroactive Steroid Pregnenolone Sulfate Stimulates the Release of Gonadotropin-Releasing Hormone from GT1-7 Hypothalamic Neurons, through N-Methyl-D-Aspartate Receptors
Endocrinology, June 1, 2006; 147(6): 2737 - 2743.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
J. Pielecka and S. M. Moenter
Effect of Steroid Milieu on Gonadotropin-Releasing Hormone-1 Neuron Firing Pattern and Luteinizing Hormone Levels in Male Mice
Biol Reprod, May 1, 2006; 74(5): 931 - 937.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. Pielecka, S. D. Quaynor, and S. M. Moenter
Androgens Increase Gonadotropin-Releasing Hormone Neuron Firing Activity in Females and Interfere with Progesterone Negative Feedback
Endocrinology, March 1, 2006; 147(3): 1474 - 1479.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. R. Ojeda, A. Lomniczi, C. Mastronardi, S. Heger, C. Roth, A.-S. Parent, V. Matagne, and A. E. Mungenast
Minireview: The Neuroendocrine Regulation of Puberty: Is the Time Ripe for a Systems Biology Approach?
Endocrinology, March 1, 2006; 147(3): 1166 - 1174.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. B. Roberts, J. A. Best, and K. J. Suter
Dendritic Processing of Excitatory Synaptic Input in Hypothalamic Gonadotropin Releasing-Hormone Neurons
Endocrinology, March 1, 2006; 147(3): 1545 - 1555.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
A. Lomniczi, A. Cornea, M. E. Costa, and S. R. Ojeda
Hypothalamic Tumor Necrosis Factor-{alpha} Converting Enzyme Mediates Excitatory Amino Acid-Dependent Neuron-to-Glia Signaling in the Neuroendocrine Brain
J. Neurosci., January 4, 2006; 26(1): 51 - 62.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. M. Moenter and R. A. DeFazio
Endogenous {gamma}-Aminobutyric Acid Can Excite Gonadotropin-Releasing Hormone Neurons
Endocrinology, December 1, 2005; 146(12): 5374 - 5379.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
Z. Chu and S. M. Moenter
Endogenous Activation of Metabotropic Glutamate Receptors Modulates GABAergic Transmission to Gonadotropin-Releasing Hormone Neurons and Alters Their Firing Rate: A Possible Local Feedback Circuit
J. Neurosci., June 15, 2005; 25(24): 5740 - 5749.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. C. Mitchell, X. F. Li, L. Breen, J.-C. Thalabard, and K. T. O'Byrne
The Role of the Locus Coeruleus in Corticotropin-Releasing Hormone and Stress-Induced Suppression of Pulsatile Luteinizing Hormone Secretion in the Female Rat
Endocrinology, January 1, 2005; 146(1): 323 - 331.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
S. D. Sullivan and S. M. Moenter
GABAergic Integration of Progesterone and Androgen Feedback to Gonadotropin-Releasing Hormone Neurons
Biol Reprod, January 1, 2005; 72(1): 33 - 41.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
A.-S. Parent, M.-C. Lebrethon, A. Gerard, and J.-P. Bourguignon
Factors Accounting for Perinatal Occurrence of Pulsatile Gonadotropin-Releasing Hormone Secretion In Vitro in Rats
Biol Reprod, January 1, 2005; 72(1): 143 - 149.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
E. N. Ottem, J. G. Godwin, S. Krishnan, and S. L. Petersen
Dual-Phenotype GABA/Glutamate Neurons in Adult Preoptic Area: Sexual Dimorphism and Function
J. Neurosci., September 15, 2004; 24(37): 8097 - 8105.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. D. Sullivan and S. M. Moenter
Prenatal androgens alter GABAergic drive to gonadotropin-releasing hormone neurons: Implications for a common fertility disorder
PNAS, May 4, 2004; 101(18): 7129 - 7134.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. D. Sullivan and S. M. Moenter
{gamma}-Aminobutyric Acid Neurons Integrate and Rapidly Transmit Permissive and Inhibitory Metabolic Cues to Gonadotropin-Releasing Hormone Neurons
Endocrinology, March 1, 2004; 145(3): 1194 - 1202.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
C. Xu, X.-Z. Xu, C. S. Nunemaker, and S. M. Moenter
Dose-Dependent Switch in Response of Gonadotropin-Releasing Hormone (GnRH) Neurons to GnRH Mediated through the Type I GnRH Receptor
Endocrinology, February 1, 2004; 145(2): 728 - 735.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S.-K. Han, M. G. Todman, and A. E. Herbison
Endogenous GABA Release Inhibits the Firing of Adult Gonadotropin-Releasing Hormone Neurons
Endocrinology, February 1, 2004; 145(2): 495 - 499.
[Abstract] [Full Text] [PDF]

Home page
 Biol. Reprod.Home page
G. L. Jackson and D. Kuehl
Effects of Applying Gamma-Aminobutyric AcidB Drugs into the Medial Basal Hypothalamus on Basal Luteinizing Hormone Concentrations and on Luteinizing Hormone Surges in the Female Sheep
Biol Reprod, February 1, 2004; 70(2): 334 - 339.
[Abstract] [Full Text] [PDF]

Home page
 Hum Reprod UpdateHome page
T. M. Plant and M. L. Barker-Gibb
Neurobiological mechanisms of puberty in higher primates
Hum. Reprod. Update, January 1, 2004; 10(1): 67 - 77.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. D. Sullivan and S. M. Moenter
Neurosteroids Alter {gamma}-Aminobutyric Acid Postsynaptic Currents in Gonadotropin-Releasing Hormone Neurons: A Possible Mechanism for Direct Steroidal Control
Endocrinology, October 1, 2003; 144(10): 4366 - 4375.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S. D. Sullivan, R. A. DeFazio, and S. M. Moenter
Metabolic Regulation of Fertility through Presynaptic and Postsynaptic Signaling to Gonadotropin-Releasing Hormone Neurons
J. Neurosci., September 17, 2003; 23(24): 8578 - 8585.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
H. T. Jansen, C. Cutter, S. Hardy, M. N. Lehman, and R. L. Goodman
Seasonal Plasticity within the Gonadotropin-Releasing Hormone (GnRH) System of the Ewe: Changes in Identified GnRH Inputs and Glial Association
Endocrinology, August 1, 2003; 144(8): 3663 - 3676.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. M. Leupen, S. A. Tobet, W. F. Crowley Jr., and K. Kaila
Heterogeneous Expression of the Potassium-Chloride Cotransporter KCC2 in Gonadotropin-Releasing Hormone Neurons of the Adult Mouse
Endocrinology, July 1, 2003; 144(7): 3031 - 3036.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
S. Heger, M. Seney, E. Bless, G. A. Schwarting, M. Bilger, A. Mungenast, S. R. Ojeda, and S. A. Tobet
Overexpression of Glutamic Acid Decarboxylase-67 (GAD-67) in Gonadotropin-Releasing Hormone Neurons Disrupts Migratory Fate and Female Reproductive Function in Mice
Endocrinology, June 1, 2003; 144(6): 2566 - 2579.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2002 by The Endocrine Society