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.
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http://dx.doi.org/10.3389/fnins.2014.00387 | DOI Listing |
Physiol Rev
January 2025
Department of Investigative Medicine, Imperial College London, Hammersmith Hospital, London, United Kingdom.
Kisspeptin and neurokinin B (NKB) play a key role in several physiological processes including in puberty, adult reproductive function including the menstrual cycle, as well as mediating the symptoms of menopause. Infundibular kisspeptin neurons, which co-express NKB, regulate the activity of gonadotropin releasing hormone (GnRH) neurons, and thus the physiological pulsatile secretion of GnRH from the hypothalamus. Outside of their hypothalamic reproductive roles, these peptides are implicated in several physiological functions including sexual behavior and attraction, placental function, and bone health.
View Article and Find Full Text PDFElife
January 2025
Department of Physiology, Development and Neuroscience, Downing site, University of Cambridge, Cambridge, United Kingdom.
The gonadotropin-releasing hormone (GnRH) neurons represent the key output cells of the neural network controlling mammalian fertility. We used GCaMP fiber photometry to record the population activity of the GnRH neuron distal projections in the ventral arcuate nucleus where they merge before entering the median eminence to release GnRH into the portal vasculature. Recordings in freely behaving intact male and female mice revealed abrupt ~8 min duration increases in activity that correlated perfectly with the appearance of a subsequent pulse of luteinizing hormone (LH).
View Article and Find Full Text PDFElife
January 2025
Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
J Neurosci
January 2025
Laboratory of Reproductive Neurobiology, Hun-Ren Institute of Experimental Medicine, Budapest, 1083 Hungary;
While hypothalamic kisspeptin (KP) neurons play well-established roles in the estrogen-dependent regulation of reproduction, little is known about extrahypothalamic KP-producing (KP) neurons of the lateral septum. As established previously, expression in this region is low and regulated by estrogen receptor- and GABA receptor-dependent mechanisms. Our present experiments on knock-in mice revealed that transgene expression in the LS begins at P33-36 in females and P40-45 in males and is stimulated by estrogen receptor signaling.
View Article and Find Full Text PDFMetabolism
December 2024
Instituto Maimónides de Investigación Biomédica de Cordoba (IMIBIC), Department of Cell Biology, Physiology and Immunology, University of Cordoba; and Hospital Universitario Reina Sofia, Cordoba, Spain; CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain. Electronic address:
Female reproduction is highly sensitive to body energy stores; persistent energy deficit, as seen in anorexia or strenuous exercise, is known to suppress ovulation via ill-defined mechanisms. We report herein that hypothalamic SIRT1, a key component of the epigenetic machinery that links nutritional status and puberty onset via modulation of Kiss1, plays a critical role in the control of the preovulatory surge of gonadotropins, i.e.
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