Neuropeptide Y Directly Inhibits Neuronal Activity in a Subpopulation of Gonadotropin-Releasing Hormone-1 Neurons via Y1 Receptors

Abstract

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.

Leptin Signaling in GABA Neurons, But Not Glutamate Neurons, Is Required for Reproductive Function

“…Second, agouti-related peptide (AgRP)/neuropeptide Y (NPY) neurons in the Arc are affected by the knock-out of LEPR because they are GABAergic (Horvath et al, 1997). Both the AgRP and NPY neuropeptides have been linked to metabolic control of reproduction by direct actions onto GnRH neurons (Klenke et al, 2010;Roa and Herbison, 2012) and indirectly by inhibiting the stimulatory ␣ melanocyte-stimulating hormone produced from the Pomc gene (Israel et al, 2012). In both leptindeficient ob/ob and LEPR-deficient db/db animals, ablation of AgRP neurons restores normal puberty onset and fertility (Israel et al, 2012;Wu et al, 2012).…”

“…The cell bodies of GnRH neurons are innervated by glutamatergic terminals that stimulate GnRH release (Bourguignon et al, 1995;Kiss et al, 2003). Hypothalamic glutamatergic LEPR neurons can be found in the Arc, the ventral medial nucleus (VMN), and the ventral premammilary nucleus (PMV) Vong et al, 2011).…”

SDF and GABA interact to regulate axophilic migration of GnRH neurons

“…However, SDF-1 also activates GIRK channels (Guyon et al, 2005;Guyon and Nahon, 2007) which GnRH neurons express (Hu et al, 2006;Klenke et al, 2010). To delineate the SDF-1/CXCR4 signaling pathway altering GnRH neuronal movement, experiments were performed using 1) v-Conotoxin, an inhibitor of N-type Ca 2+ channels and 2) tertiapin Q (TPN-Q), an inhibitor of GIRK channels (Klenke et al, 2010).…”

Polymorphisms associated with egg number at 300 days of age in chickens

“…GnRH, binding with its receptor GnRHR, stimulates gonadotrophin secretion from the pituitary gland and then evokes steroidogenesis in the gonads, resulting in egg production in hens (Shacham et al, 2001;Proudman et al, 2006;Sonez et al, 2010). Neuropeptide Y (NPY) is known to be involved in the regulation of reproductive function at the hypothalamic level through the control of GnRH secretion (Dhillon et al, 2009;Klenke et al, 2010). Beside this GnRH-gonadotrophin pathway, avian seasonal reproduction is also controlled by the vasoactive intestinal peptide (VIP) -prolactin (PRL) neuroendocrine pathway (Sharp, 2005;Leska and Dusza, 2007).…”