title: Glutamatergic and GABAergic innervation of human gonadotropin-releasing hormone-I neurons.
abstract: Amino acid (aa) neurotransmitters in synaptic afferents to hypothalamic GnRH-I neurons are critically involved in the neuroendocrine control of reproduction. Although in rodents the major aa neurotransmitter in these afferents is γ-aminobutyric acid (GABA), glutamatergic axons also innervate GnRH neurons directly. Our aim with the present study was to address the relative contribution of GABAergic and glutamatergic axons to the afferent control of human GnRH neurons. Formalin-fixed hypothalamic samples were obtained from adult male individuals (n = 8) at autopsies, and their coronal sections processed for dual-label immunohistochemical studies. GABAergic axons were labeled with vesicular inhibitory aa transporter antibodies, whereas glutamatergic axons were detected with antisera against the major vesicular glutamate transporter (VGLUT) isoforms, VGLUT1 and VGLUT2. The relative incidences of GABAergic and glutamatergic axonal appositions to GnRH-immunoreactive neurons were compared quantitatively in two regions, the infundibular and paraventricular nuclei. Results showed that GABAergic axons established the most frequently encountered type of axo-somatic apposition. Glutamatergic contacts occurred in significantly lower numbers, with similar contributions by their VGLUT1 and VGLUT2 subclasses. The innervation pattern was different on GnRH dendrites where the combined incidence of glutamatergic (VGLUT1 + VGLUT2) contacts slightly exceeded that of the GABAergic appositions. We conclude that GABA represents the major aa neurotransmitter in axo-somatic afferents to human GnRH neurons, whereas glutamatergic inputs occur somewhat more frequently than GABAergic inputs on GnRH dendrites. Unlike in rats, the GnRH system of the human receives innervation from the VGLUT1, in addition to the VGLUT2, subclass of glutamatergic neurons.
authors.affiliation: Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary. hrabovszky.erik@koki.hu
authors.forename: Erik
authors.initials: E
authors.lastname: Hrabovszky
authors.forename: Csilla S
authors.initials: CS
authors.lastname: Molnár
authors.forename: Róbert
authors.initials: R
authors.lastname: Nagy
authors.forename: Barbara
authors.initials: B
authors.lastname: Vida
authors.forename: Beáta Á
authors.initials: BÁ
authors.lastname: Borsay
authors.forename: Kálmán
authors.initials: K
authors.lastname: Rácz
authors.forename: László
authors.initials: L
authors.lastname: Herczeg
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Imre
authors.initials: I
authors.lastname: Kalló
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Liposits
mesh_terms: D000328:Adult; D000368:Aged; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism; D001344:Autopsy; D001369:Axons / Q000378:metabolism / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism / Q000502:physiology; D005971:Glutamates / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D005971:Glutamates; D011498:Protein Precursors; C493476:SLC17A6 protein, human; C493464:SLC17A7 protein, human; C492245:SLC32A1 protein, human; D050598:Vesicular Glutamate Transport Protein 1; D050599:Vesicular Glutamate Transport Protein 2; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C050866:progonadoliberin I; D007987:Gonadotropin-Releasing Hormone; D005680:gamma-Aminobutyric Acid