Neuropeptide Y directly inhibits neuronal activity in a subpopulation of gonadotropin-releasing hormone-1 neurons via Y1 receptors.
Neuropeptide Y (NPY), a member of the pancreatic polypeptide family, is an orexigenic hormone. GnRH-1 neurons express NPY receptors. This suggests a direct link between metabolic function and reproduction. However, the effect of NPY on GnRH-1 cells has been variable, dependent on metabolic and reproductive status of the animal. This study circumvents these issues by examining the role of NPY on GnRH-1 neuronal activity in an explant model that is based on the extra-central nervous system origin of GnRH-1 neurons. These prenatal GnRH-1 neurons express many receptors found in GnRH-1 neurons in the brain and use similar transduction pathways. In addition, these GnRH-1 cells exhibit spontaneous and ligand-induced oscillations in intracellular calcium as well as pulsatile calcium-controlled GnRH-1 release. Single-cell PCR determined that prenatal GnRH-1 neurons express the G protein-coupled Y1 receptor (Y1R). To address the influence of NPY on GnRH-1 neuronal activity, calcium imaging was used to monitor individual and population dynamics. NPY treatment, mimicked with Y1R agonist, significantly decreased the number of calcium peaks per minute in GnRH-1 neurons and was prevented by a Y1R antagonist. Pertussis toxin blocked the effect of NPY on GnRH-1 neuronal activity, indicating the coupling of Y1R to inhibitory G protein. The NPY-induced inhibition was independent of the adenylate cyclase pathway but mediated by the activation of G protein-coupled inwardly rectifying potassium channels. These results indicate that at an early developmental stage, GnRH-1 neuronal activity can be directly inhibited by NPY via its Y1R.
Klenke
Ulrike
U
Cellular and Developmental Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
Constantin
Stephanie
S
Wray
Susan
S
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004622:Embryo, Mammalian; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009478:Neuropeptide Y / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
C092926:BIBP 3226; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D007987:Gonadotropin-Releasing Hormone; D001120:Arginine; D000262:Adenylyl Cyclases; D002118:Calcium