Neuropeptide Y induces gonadotropin-releasing hormone gene expression directly and through conditioned medium from mHypoE-38 NPY neurons

Dhillon, Sandeep; Gingerich, Sarah; Belsham, Denise D.

doi:10.1016/j.regpep.2009.04.005

Cited by 18 publications

(8 citation statements)

References 58 publications

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“…In contrast, the mHypoE-42 cells were identified as a feeding-related NPY neuron because treatment with estrogen steadily repressed NPY mRNA expression to potentially exert anorexigenic effects. A subsequent study in our lab also found that conditioned media containing NPY synthesized from the mHypoE-38 cells significantly stimulated GnRH mRNA expression in the GT1-7 cell line, a GnRH neuronal model (35). We further characterized the mHypoE-38 and mHypoE-42 cell lines in the present study.…”

Section: Figsupporting

confidence: 55%

Kisspeptin Directly Regulates Neuropeptide Y Synthesis and Secretion via the ERK1/2 and p38 Mitogen-Activated Protein Kinase Signaling Pathways in NPY-Secreting Hypothalamic Neurons

2010

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Kisspeptin is a key component of reproduction that directly stimulates GnRH neurons. However, recent studies indicate that kisspeptin can indirectly stimulate GnRH neurons through unidentified afferent networks. Neuropeptide Y (NPY) is another key reproductive hormone that is an afferent stimulator of GnRH neurons. Herein, we report kisspeptin receptor Kiss1r mRNA expression in native NPY neurons FAC-sorted from NPY-GFP transgenic mice. Thus, we hypothesized that kisspeptin indirectly stimulates GnRH neurons through direct regulation of NPY neurons. Using hypothalamic NPY-secreting cell lines, we determined that kisspeptin stimulates NPY mRNA expression and secretion in the mHypoE-38 cells, but not the mHypoE-42 cells, using quantitative RT-PCR and enzyme immunoassays. Furthermore, agouti-related peptide, ghrelin, neurotensin, or Kiss1r mRNA expression was not changed upon exposure to kisspeptin in either cell line. These results concur with our previous work identifying the mHypoE-38 cell line as a putative reproductive NPY neuron and the mHypoE-42 cell line as a potential feeding-related NPY neuron. In the mHypoE-38 cells, kisspeptin activated the ERK1/2 and p38 MAPK kinases as shown by Western blot analysis. Moreover, inhibiting the ERK1/2 and p38 pathways with U0126 and SB239063, respectively, prevented kisspeptin induction of NPY mRNA expression and secretion. Altogether, we find that kisspeptin directly regulates NPY synthesis and secretion via the ERK1/2 and p38 MAPK pathways in a NPY-secreting cell line, and we propose NPY neurons as an afferent network by which kisspeptin indirectly stimulates GnRH secretion. (Endocrinology 151: 5038 -5047, 2010)

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Section: Figsupporting

confidence: 55%

Kisspeptin Directly Regulates Neuropeptide Y Synthesis and Secretion via the ERK1/2 and p38 Mitogen-Activated Protein Kinase Signaling Pathways in NPY-Secreting Hypothalamic Neurons

2010

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“…Using GT1-7 neurons, which express the Y1, -2, and -4 (62), our group demonstrated that NPY triggers an increase in GnRH mRNA expression in GnRH neurons via activation of the Y1 receptor and of the downstream PKA and MAPK pathways. This study sheds light on the potential mechanisms involved in NPY regulation of the GnRH neuron and suggests that NPY stimulates GnRH secretion via an increase in GnRH production (62).…”

Section: New Insights Into Reproduction Using Neuronal Cell Modelsmentioning

confidence: 79%

Immortalized neurons for the study of hypothalamic function

Dalvi

Nazarians-Armavil

Tung

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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The hypothalamus is a vital part of the central nervous system: it harbors control systems implicated in regulation of a wide range of homeostatic processes, including energy balance and reproduction. Structurally, the hypothalamus is a complex neuroendocrine tissue composed of a multitude of unique neuronal cell types that express a number of neuromodulators, including hormones, classical neurotransmitters, and specific neuropeptides that play a critical role in mediating hypothalamic function. However, neuropeptide and receptor gene expression, second messenger activation, and electrophysiological and secretory properties of these hypothalamic neurons are not yet fully defined, primarily because the heterogeneity and complex neuronal architecture of the neuroendocrine hypothalamus make such studies challenging to perform in vivo. To circumvent this problem, our research group recently generated embryonic- and adult-derived hypothalamic neuronal cell models by utilizing the novel molecular techniques of ciliary neurotrophic factor-induced neurogenesis and SV40 T antigen transfer to primary hypothalamic neuronal cell cultures. Significant research with these cell lines has demonstrated their value as a potential tool for use in molecular genetic analysis of hypothalamic neuronal function. Insights gained from hypothalamic immortalized cells used in conjunction with in vivo models will enhance our understanding of hypothalamic functions such as neurogenesis, neuronal plasticity, glucose sensing, energy homeostasis, circadian rhythms, and reproduction. This review discusses the generation and use of hypothalamic cell models to study mechanisms underlying the function of individual hypothalamic neurons and to gain a more complete understanding of the overall physiology of the hypothalamus.

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“…For example, NPY has a biphasic modulatory effect on [Ca 2+ ] i increases induced by ATP, mediates the upregulated mRNA expression of gonadotropin-releasing hormone in a neuroblastoma cell line and induces cathecolamine release in human adrenal chromaffin cells, through the activation of PKA. 52, 53, 54 However, there is also evidence showing that NPY inhibits PKA. The activation of NPY receptors inhibits both the axonal transport in sensory neurons and cell proliferation in vascular smooth muscle cells, with these effects being mediated by PKA inhibition.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y receptors activation protects rat retinal neural cells against necrotic and apoptotic cell death induced by glutamate

et al. 2013

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It has been claimed that glutamate excitotoxicity might have a role in the pathogenesis of several retinal degenerative diseases, including glaucoma and diabetic retinopathy. Neuropeptide Y (NPY) has neuroprotective properties against excitotoxicity in the hippocampus, through the activation of Y1, Y2 and/or Y5 receptors. The principal objective of this study is to investigate the potential protective role of NPY against glutamate-induced toxicity in rat retinal cells (in vitro and in an animal model), unraveling the NPY receptors and intracellular mechanisms involved. Rat retinal neural cell cultures were prepared from newborn Wistar rats (P3-P5) and exposed to glutamate (500 μM) for 24 h. Necrotic cell death was evaluated by propidium iodide (PI) assay and apoptotic cell death using TUNEL and caspase-3 assays. The cell types present in culture were identified by immunocytochemistry. The involvement of NPY receptors was assessed using selective agonists and antagonists. Pre-treatment of cells with NPY (100 nM) inhibited both necrotic cell death (PI-positive cells) and apoptotic cell death (TUNEL-positive cells and caspase 3-positive cells) triggered by glutamate, with the neurons being the cells most strongly affected. The activation of NPY Y2, Y4 and Y5 receptors inhibited necrotic cell death, while apoptotic cell death was only prevented by the activation of NPY Y5 receptor. Moreover, NPY neuroprotective effect was mediated by the activation of PKA and p38K. In the animal model, NPY (2.35 nmol) was intravitreally injected 2 h before glutamate (500 nmol) injection into the vitreous. The protective role of NPY was assessed 24 h after glutamate (or saline) injection by TUNEL assay and Brn3a (marker of ganglion cells) immunohistochemistry. NPY inhibited the increase in the number of TUNEL-positive cells and the decrease in the number of Brn3a-positive cells induced by glutamate. In conclusion, NPY and NPY receptors can be considered potential targets to treat retinal degenerative diseases, such as glaucoma and diabetic retinopathy.

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Neuropeptide Y induces gonadotropin-releasing hormone gene expression directly and through conditioned medium from mHypoE-38 NPY neurons

Cited by 18 publications

References 58 publications

Kisspeptin Directly Regulates Neuropeptide Y Synthesis and Secretion via the ERK1/2 and p38 Mitogen-Activated Protein Kinase Signaling Pathways in NPY-Secreting Hypothalamic Neurons

Kisspeptin Directly Regulates Neuropeptide Y Synthesis and Secretion via the ERK1/2 and p38 Mitogen-Activated Protein Kinase Signaling Pathways in NPY-Secreting Hypothalamic Neurons

Immortalized neurons for the study of hypothalamic function

Neuropeptide Y receptors activation protects rat retinal neural cells against necrotic and apoptotic cell death induced by glutamate

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