The DOI matches its Crossref record; 109 of the 111 references it cites were found in a registry or an index.
The role of GABA in the regulation of GnRH neurons
Open accessAbstract
Gonadotropin-releasing hormone (GnRH) neurons form the final common pathway for the central regulation of reproduction. Gamma-amino butyric acid (GABA) has long been implicated as one of the major players in the regulation of GnRH neurons. Although GABA is typically an inhibitory neurotransmitter in the mature adult central nervous system, most mature GnRH neurons show the unusual characteristic of being excited by GABA. While many reports have provided much insight into the contribution of GABA to the activity of GnRH neurons, the precise physiological role of the excitatory action of GABA on GnRH neurons remains elusive. This brief review presents the current knowledge of the role of GABA signaling in GnRH neuronal activity. We also discuss the modulation of GABA signaling by neurotransmitters and neuromodulators and the functional consequence of GABAergic inputs to GnRH neurons in both the physiology and pathology of reproduction.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Figures
![Figure 1 Excitatory action of GABA on rat GnRH neurons. (A) Representative [Ca2+]i response to 100 μM GABA. Most GnRH neurons showed [Ca2+]i increase in response to GABA. Some GnRH neurons did not respond to GABA. Some GnRH neurons showed [Ca2+]i decrease in response to GABA. (B) Muscimol (100 μM), a GABAA receptor agonist, increased [Ca2+]i in GnRH neurons. (C) Bicuculline (100 μM), a GABAA receptor antagonist, inhibited the [Ca2+]i increase induced by GABA. (D) GABA-induced [Ca2+]i increase was inhibited in Ca2+-free solution. (E) Bumetanide (100 μM), a blocker of NKCC1, reduced the GABA-induced [Ca2+]i increase. Muscimol and GABA were applied as indicated with horizontal bars. Bicuculline, Ca2+-free solution, and bumetanide were applied as indicated with open bars (Originally published in Watanabe et al., 2009a).](/paper-figures/b6dc525df0714f33b51414cfbc631b19/the-role-of-gaba-in-the-regulation-of-gnrh-neurons-figure-1.jpg)
![Figure 2 The intracellular Cl− concentration determines the polarity of GABA response. The GABA action is excitatory in immature neurons because [Cl−]i is high, owing to high levels of the Na+-K+-2Cl− cotransporter (NKCC1), which mediates inward transport of Cl−, and to low levels of the K+-Cl− cotransporter (KCC2), which excludes Cl− from the cell. In most neurons, the GABA response switches from excitation to inhibition during early postnatal development, due to the developmental decrease of the NKCC1 and increase of the KCC2. However, even in the mature neurons, neuronal damage down regulates the KCC2 and elevated Cl− concentration shifts GABA response from hyperpolarization to depolarization, occasionally excitation. Most GnRH neurons show the unusual characteristic of being excited by GABA in the adult brain.](/paper-figures/c9087b02279c499c8292653fc7d55f9d/the-role-of-gaba-in-the-regulation-of-gnrh-neurons-figure-2.jpg)
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“The activity of GnRH is regulated by neurotransmitters, steroid hormones, and growth factors (Watanabe, Fukuda, & Nabekura, 2014).”
From Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity (2017) · cites this paper as Watanabe, Fukuda, & Nabekura, 2014
The cited source says what the claim attributes to it.
In the citing paper
“Different data converge to indicate that the LH surge is stimulated by glutamate [102,103] and inhibited by GABA [104,105]”
From Fibromyalgia pathogenesis explained by a neuroendocrine multistable model (2024) · cites this paper as [104]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,951
Excitatory actions of gaba during development: the nature of the nurture
Ben-Ari, Y. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn920 · Cited by 2,448
Messager, S., Chatzidaki, E. E., Ma, D., Hendrick, A. G., Zahn, D., Dixon, J., Thresher, R. R., Malinge, I., Lomet, D., Carlton, M. B. L., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409330102 · Cited by 1,242
A role for kisspeptins in the regulation of gonadotropin secretion in the mouse
Gottsch, M. L., Cunningham, M. J., Smith, J. T., Popa, S. M., Acohido, B. V., Crowley, W. F., Seminara, S., Clifton, D. K., & Steiner, R. A. (2004) · Endocrinology · doi:10.1210/en.2004-0431 · Cited by 1,161
Han, S.-K., Gottsch, M. L., Lee, K. J., Popa, S. M., Smith, J. T., Jakawich, S. K., Clifton, D. K., Steiner, R. A., & Herbison, A. E. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.3328-05.2005 · Cited by 1,036
Immortalization of hypothalamic GnRH by genetically targeted tumorigenesis
Mellon, P. L., Windle, J. J., Goldsmith, P. C., Padula, C. A., Roberts, J. L., & Weiner, R. I. (1990) · Neuron · doi:10.1016/0896-6273(90)90028-e · Cited by 960
Cation-Chloride Cotransporters and Neuronal Function
Blaesse, P., Airaksinen, M. S., Rivera, C., & Kaila, K. (2009) · Neuron · doi:10.1016/j.neuron.2009.03.003 · Cited by 860
Two isoforms of glutamate decarboxylase: why?
Soghomonian, J., & Martin, D. L. (1998) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(98)01270-x · Cited by 643
Mechanism of Activity-Dependent Downregulation of the Neuron-Specific K-Cl Cotransporter KCC2
Rivera, C., Voipio, J., Thomas-Crusells, J., Li, H., Emri, Z., Sipilä, S., Payne, J. A., Minichiello, L., Saarma, M., & Kaila, K. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.5265-03.2004 · Cited by 515
Roles of the cation–chloride cotransporters in neurological disease
Kahle, K. T., Staley, K. J., Nahed, B. V., Gamba, G., Hébert, S., Lifton, R. P., & Mount, D. B. (2008) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0883 · Cited by 430
Cited by
Sorted by citations
Items 101–144 of 144
Rani, R., Sri, N. S., Medishetti, R., Chatti, K., & Sevilimedu, A. (2024) · Human Molecular Genetics · doi:10.1093/hmg/ddae077 · Cited by 1
Li, J., Zhu, S., & Shi, F. (2025) · Food and Chemical Toxicology · doi:10.1016/j.fct.2025.115522 · Cited by 1
Reversal of Congenital Hypogonadotropic Hypogonadism
Dwyer, A. A., & Stamou, M. I. (2025) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaf610 · Cited by 2
Mei, Y., Yan, Y., Ke, S., Su, W., Luo, Z., Chen, X., Xu, H., Su, W., & Li, A. (2026) · Toxics · doi:10.3390/toxics14010055 · Cited by 1
“(3 ) Homocysteine pathway: N-methyl-D-aspartate (NMDA) stimulates the release of FSH and LH [59], while gamma-aminobutyric acid (GABA) plays an important role in regulating the activity of GnRH neurons [60].”
Mota, L. F. M., Arikawa, L. M., Santos, D. J. A., Brito, L. F., Fonseca, L. F. S., Oliveira, H. N., & Albuquerque, L. G. (2026) · Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · doi:10.1186/s40104-026-01428-5 · Cited by 1
“Because GABAergic neurons regulate pulsatile GnRH release [116], genetic variation in this pathway may influence how effectively animals adjust reproductive function to environmental conditions.”
InfluentialArmstrong, B., Murphy, C. A., & Basu, N. (2018) · Springer eBooks · doi:10.1007/978-3-319-66084-4_16 · Cited by 1
Microbiota and its therapeutic implications in reproductive health and diseases
Singh, P., & Srivastava, R. K. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99336-4.00003-3 · Cited by 2
Jamshidi, Z., Karami, M., Khalili, M., & Roghani, M. (2023) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/ijem.ijem_364_22 · Cited by 1
“[14] Another study has indicated that GABAB receptors regulate the excitability of GnRH neurons.”
BackgroundThe Effect of Low Level He-Ne Laser on Spawning Behavior in Common Carp Fish Cyprinus carpio
Abies, L. M., Al-Hassnawi, A. T. S., & Al-Amari, M. J. Y. (2015) · American Journal of Biology and Life Sciences · Cited by 1
Carrasco, R. A. (2016) · University Library - University of Saskatchewan (University of Saskatchewan) · Cited by 1
Early-life environment programs reproductive strategies through epigenetic regulation of SRD5A1Preprint
Bar-Sadeh, B., Eden, O., Pnueli, L., Begum, K., Leeman, G., Emes, R. D., Stöger, R. J., Bentley, G. R., & Melamed, P. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.09.16.299560 · Cited by 1
Effect of Environmental Toxicants on the Neuroendocrine Control of Female Reproduction
Farmer, W. T., & Stoker, T. E. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.95677-0
Physiopathology, Diagnosis, and Treatment of Secondary Female Hypogonadism
Antoniou-Tsigkos, A., Μacut, D., & Mastorakos, G. P. (2017) · Endocrinology · doi:10.1007/978-3-319-38681-2_9-1
Grid1 Regulates the Onset of Puberty in Female RatsPreprint
Ye, J., Qin, P., Li, H., Kang, T., Si, W., Yao, Z., Liu, Y., Yu, T., Zhang, Y., Ling, Y., et al. (2020) · Research Square · doi:10.21203/rs.3.rs-134074/v1
Functions of the GABAergic system on serum LH concentrations in pre-pubertal Nellore heifers
Cardoso, D., Cardoso, R. C., & Nogueira, G. D. P. (2021) · Animal Reproduction Science · doi:10.1016/j.anireprosci.2021.106764
The effect of a high sucrose diet on ovarian morphology : an age-matched generational study
Foiret, J. R. (2019) · SUNScholar (Stellenbosch University)
Function of folllicle stimulating hormone and the follicle stimulating hormone receptor
Whiteley, G. E., Lindner, P. G., Schmiech, K. V., & Hill, M. J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-821676-7.00019-6
Liu, B., & Ren, H.-L. (2022) · Research Square · doi:10.21203/rs.3.rs-2221014/v1
(2023) · Wiley eBooks · doi:10.1002/9781394236329.refs
Expression and localization of HPG axis-related genes in Carassius auratus with different ploidy
Xu, X., Yang, L., Deng, X., Xiao, Q., Huang, X., Wang, C., Xu, X., Zhou, Y., Luo, X., Zhang, Y., et al. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1336679
“In teleost, Gnrh2 stimulates gonadotropin release, affecting animal reproductive behavior and feeding (9 – 11).”
BackgroundImpaired ovarian development in a zebrafish fmr1 knockout modelPreprint
Rani, R., Sri, N. S., Medishetti, R., Chatti, K., & Sevilimedu, A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.10.579749
Xu, W., Mu, R., Gegen, T., Ran, T., Wu, Q., Wen, D., Wang, F., & Chen, Z. J. (2023) · Figshare · doi:10.6084/m9.figshare.24883553
Effects of Environmental Toxicants on the Neuroendocrine Control of Female Reproduction
Stoker, T. E. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.00118-2
Botanical Bounty: Exploring Aphrodisiac Drug Discovery and Development from Nature's Pharmacy
Bilal, M., Jain, D., Chaitanya, M., Khurana, N., Singh, S., Mazumder, A., & Singh, K. (2024) · Current Bioactive Compounds · doi:10.2174/0115734072334775241209052941
Beall, C., Hanna, L., & Ellacott, K. L. J. (2017) · Comprehensive physiology · doi:10.1002/j.2040-4603.2017.tb00781.x
“The neurotransmitter(s) mediating the modulation of GnRH neurons downstream of leptin-induced activation of PMv neurons are not fully elucidated but glutamate and nitric oxide have been implicated (157, 355, 595).”
Enrofloxacin exposure enhances GABA synthesis via PI3K/Akt signaling pathway in crucian carp brain
Ruan, J., Wan, G., Luo, P., Huang, J., & Liu, H. (2025) · Scientific Reports · doi:10.1038/s41598-025-06260-x
Cardiac activity and the influence of isoflurane on this parameter in Anteos menippe butterfliesPreprint
Júnior, A. B. G., Cardoso, D. D. L., Kondo, S. R. S., Lins, A., Hayasaki, N. D. C., Zamian, E. M. D. S., de Assis, A. C. L., Felix, D. M., Viana, E. V. F., da Paz, C. A., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-8022097/v1
Xu, W., Mu, R., Gegen, T., Ran, T., Wu, Q., Wen, D., Wang, F., & Chen, Z. (2024) · Figshare · doi:10.6084/m9.figshare.26656855
Xu, W., Mu, R., Gegen, T., Ran, T., Wu, Q., Wen, D., Wang, F., & Chen, Z. (2024) · Figshare · doi:10.6084/m9.figshare.24883817
Xu, W., Mu, R., Gegen, T., Ran, T., Wu, Q., Wen, D., Wang, F., & Chen, Z. (2024) · Figshare · doi:10.6084/m9.figshare.26656858
Manizheh, H., Mahmoudi, F., Haghighat, K., & Khazali, H. (2025) · Reports of Biochemistry and Molecular Biology · doi:10.61882/rbmb.14.1.38
Metabolites as signaling molecules: indispensable roles in the regulation of embryo implantation
Wu, J., Xu, M., Zhao, S.-M., & Yuan, Y.-Y. (2026) · Reproductive and Developmental Medicine · doi:10.1097/rd9.0000000000000158
Sun, X., Yuanze, G., Zhang, L., Li, W., Ning, A., Ganesan, K., Li, Z., Zhang, X., Liu, H., Wang, L., et al. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.121623
IMPACT DE L’HYPERCORTICISME SUR L’AXE GONADOTROPE FEMELLE
Ayrout, M. (2018) · theses.fr (ABES) · doi:10.70675/194a6ff5z99f6z4ef0z800ez5473528e7a30
Perturbation de la rythmicité circadienne : impact sur la fonction reproductive de souris femelles
Bahougne, T. (2020) · theses.fr (ABES) · doi:10.70675/f27b711fz7b99z44f6za0c5zaea6ee95b797
Franssen, D., & Kaiser, U. B. (2026) · Current Opinion in Pediatrics · doi:10.1097/mop.0000000000001588
Kotula‐Balak, M., Uyar, R., Morańska, E., Lonc, G., Boztepe, Ü. G., & Łopuszyński, W. (2026) · Animals · doi:10.3390/ani16132005
The endogenous ghrelin antagonist, LEAP2, accelerates puberty onset in conditions of early obesity
Torres-Granados, C., Morris, P. G., Ruiz-Cruz, M., Pomares, O., Guerrero‐Ruiz, Y., Uceda‐Rodriguez, E., Rodríguez-Vázquez, E., Torrecillas, Á. A., Garcés, C., Gaytán, F., et al. (2026) · Metabolism · doi:10.1016/j.metabol.2026.156695
Reproduction under Siege: How Chronic Stress Hijacks the HPG Axis?
Xu, D., Zhao, X., Chen, W., Liu, Y., & Wang, C. (2026) · Neuroendocrinology · doi:10.1159/000553429 · Cited by 2
Hotha, A., & Ganesh, C. B. (2026) · Fish Physiology and Biochemistry · doi:10.1007/s10695-026-01747-4
“For example, GABA receptors are expressed on GnRH neurosecretory neurons as well as on upstream GABAergic interneurons that synaptically regulate these cells in vertebrates (Watanabe et al. 2014).”
Pan, Z., Zhang, W., Han, K., Fu, D., Jiang, X., Li, M., Liu, Y., Li, Y., & Fang, F. (2026) · Theriogenology · doi:10.1016/j.theriogenology.2026.118260
Metadata
- Authors
- Watanabe, M., Fukuda, A., & Nabekura, J.
- Affiliations
- Hamamatsu University (JP)
- The Graduate University for Advanced Studies, SOKENDAI (JP)
- Corresponding author
- Watanabe, Miho
- Venue
- Frontiers in Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2014-11-28
- Volume
- 8
- Pages
- 387-387
- ISSN
- 1662-453X (ISSN-L)
- PMC
- PMC4246667
- OpenAlex
- W2135581544
- Cited by
- 140
- References
- 111
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 12 · 2023: 12 · 2022: 12 · 2021: 12 · 2020: 17 · 2019: 13 · 2018: 9 · 2017: 12 · 2016: 10 · 2015: 9
- FWCI
- 1.63
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Society for the Promotion of Science (26670512, 25460312, 25293052)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Keywords
- GABA, GnRH neurons, GABAergic inhibition, neuroendocrine regulation of reproduction, neurotransmitter modulation, neuromodulators, GABA receptors, reproductive physiology, reproductive disorders
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
