Novel Aspects of Glutamatergic Signalling in the Neuroendocrine System

Abstract

Glutamate is the principal neurotransmitter of excitatory synaptic transmission in the neuroendocrine hypothalamusIn addition to participating in normal cell metabolism, L-glutamate acts as the primary mediator of excitatory synaptic transmission in the central nervous system (1, 2). Its major contribution to the synaptic regulation of hypothalamic neuroendocrine systems has been shown by (i) the demonstration of glutamatergic asymmetric synapses on the cell bodies and dendrites of hypothalamic neurosecretory neurones, (ii) the finding of increased intracellular Ca 2+ in medial hypothalamic neurones grown in monolayer, in response to glutamate and the non-NMDA glutamate receptor agonists kainate and quisqualate, and finally (iii) the observation that the non-NMDA glutamate antagonist CNQX decreased the electrically stimulated and spontaneous excitatory postsynaptic potentials in acute hypothalamic slice preparations (3). Ionotropic and metabotropic receptors mediate glutamate actionsGlutamate receptors that form cation channels fall into the category of ionotropic receptors. Based on their binding affinities for prototypical ligands, they are further categorised as kainate, AMPA and NMDA receptors (4-7). Metabotropic glutamate receptors (mGluR1-8), in turn, comprise a unique family of G-protein coupled receptors that can be classified into three groups (groups I-III) based on G-protein coupling specificity and sequence similarity (7-10). Journal of NeuroendocrinologyCorrespondence to: Zsolt Liposits, Laboratory of Endocrine Neurobiology, Institute of Experimental Medicine, P.O. Box 67, 1450 Budapest, Hungary (e-mail: liposits@koki.hu).L-glutamate, the main excitatory neurotransmitter, influences virtually all neurones of the neuroendocrine hypothalamus via synaptic mechanisms. Vesicular glutamate transporters (VGLUT1-3), which selectively accumulate L-glutamate into synaptic vesicles, provide markers with which to visualise glutamatergic neurones in histological preparations; excitatory neurones in the endocrine hypothalamus synthesise the VGLUT2 isoform. Results of recent dual-label in situ hybridisation studies indicate that glutamatergic neurones in the preoptic area and the hypothalamic paraventricular, supraoptic and periventricular nuclei include parvocellular and magnocellular neurosecretory neurones which secrete peptide neurohormones into the bloodstream to regulate endocrine functions. Neurosecretory terminals of GnRH, TRH, CRF-, somatostatin-, oxytocin-and vasopressin-secreting neurones contain VGLUT2 immunoreactivity, suggesting the co-release of glutamate with hypophysiotrophic peptides. The presence of VGLUT2 also indicates glutamate secretion from non-neuronal endocrine cells, including gonadotrophs and thyrotrophs of the anterior pituitary. Results of in vitro studies show that ionotropic glutamate receptor analogues can elicit hormone secretion at neuroendocrine ⁄ endocrine release sites. Structural constituents of the median eminence, adenohypophysis and neurohypophysis contain elements of glut...

Distribution of type 1 cannabinoid receptor‐expressing neurons in the septal‐hypothalamic region of the mouse: Colocalization with GABAergic and glutamatergic markers

“…mRNA (Hrabovszky and Liposits, 2008). In the present studies we identified large numbers of CB1/VGLUT2 dual-labeled neurons in the SO, although individually, these cells contained low CB1 mRNA levels only.…”

Nitric Oxide as Key Mediator of Neuron-to-Neuron and Endothelia-to-Glia Communication Involved in the Neuroendocrine Control of Reproduction

“…The median eminence, which lies ventrally to the third ventricle in the tuberal region of the hypothalamus, is increasingly recognized as a key site for GnRH release regulation [5,9,111,112]. Modulation of GnRH release by NO within the median eminence was suggested by early studies performed by McCann and colleagues.…”

Opposing Actions of Endothelin-1 on Glutamatergic Transmission onto Vasopressin and Oxytocin Neurons in the Supraoptic Nucleus

“…The neurohormones oxytocin (OT) and vasopressin (VP) are synthesized in the magnocellular neurosecretory cells (MNCs) of the supraoptic nucleus (SON) and paraventricular nucleus of the hypothalamus and released into the bloodstream in the posterior pituitary. Since secretion of these hormones depends on the activity of MNCs and this is tightly coupled to the efficacy of excitatory synapses (Nissen et al, 1995;Moos et al, 1997;Jourdain et al, 1998;Shibuya et al, 2000;Hrabovszky and Liposits, 2008), modulation of glutamatergic neurotransmission is an important mechanism for adjusting neuroendocrine output.…”