Neuropeptide Y (NPY) is a 36-amino acid peptide that is an abundant and widespread peptide in the mammalian nervous system. It shows sequence homology to peptide YY and over 50% homology in amino acid and nucleotide sequence to pancreatic polypeptide. Minth et al. (1984) cloned the NPY gene starting from mRNA of a pheochromocytoma.
NCBI Summary:
This gene encodes a neuropeptide that is widely expressed in the central nervous system and influences many physiological processes, including cortical excitability, stress response, food intake, circadian rhythms, and cardiovascular function. The neuropeptide functions through G protein-coupled receptors to inhibit adenylyl cyclase, activate mitogen-activated protein kinase (MAPK), regulate intracellular calcium levels, and activate potassium channels. A polymorphism in this gene resulting in a change of leucine 7 to proline in the signal peptide is associated with elevated cholesterol levels, higher alcohol consumption, and may be a risk factor for various metabolic and cardiovascular diseases. The protein also exhibits antimicrobial activity against bacteria and fungi. [provided by RefSeq, Oct 2014]
General function
Ligand, Hormone, Growth factor
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Cellular localization
Secreted
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Neuropeptide Y, leptin, galanin and insulin in women with polycystic ovary syndrome. Baranowska B et al. (2000) It has been reported that polycystic ovary syndrome (PCOS) is very frequently associated with obesity, insulin resistance and hyperinsulinemia. However, metabolic disorders may lead to suppression of reproductive hormone secretion during undernutrition and in obesity. Some neuropeptides, such as neuropeptide Y (NPY) and galanin, modulate the control of appetite and play an important role in the mechanism of luteinizing hormone-releasing hormone (LHRH) secretion. NPY and galanin regulate appetite via both central and peripheral mechanisms. The interaction between central and peripheral signals for the control of food intake is due to leptin. Leptin can modulate the activity of NPY and other peptides in the hypothalamus that are known to affect eating behavior. In order to evaluate the relationship between NPY, galanin and leptin, 28 women with PCOS, 32 obese women (non-PCOS) and 19 lean healthy women (control group) were investigated. Obese women with PCOS were divided into two groups: PCOS (A) overweight (body mass index, BMI 26-30 kg/m2), and PCOS (B) obese (BMI 31-40 kg/m2). Plasma NPY, galanin and leptin concentrations were measured by radioimmunoassay. Plasma leptin levels in obese women with PCOS (groups A and B) were significantly higher than those in the control group (p < 0.05, p < 0.05, respectively). A significant positive correlation between plasma leptin and BMI in women with PCOS was found (r = 0.427, p < 0.01). A positive correlation was demonstrated between leptin and testosterone in PCOS (r = 0.461, p < 0.01). Plasma galanin concentrations in PCOS were higher than in the control group but the differences were not significant. Plasma NPY levels were significantly elevated in both non-obese (normal) and obese women with PCOS (group A) (p < 0.01, p < 0.005, respectively). However, in obese non-PCOS women plasma NPY levels gradually increased with increase in BMI. No significant correlations were found between galanin, NPY and percentage change in response of LH to LHRH, as well as between NPY and insulin, and galanin and testosterone. Plasma insulin concentrations in women with PCOS (group B) were significantly higher than in the control group (p < 0.001). Increased plasma NPY levels are found in both obese and non-obese women with PCOS. The increase in NPY is independent of the increase in BMI. In obese women with PCOS, plasma leptin is increased compared with control lean women. Serum insulin concentration is increased in obese women with PCOS. A positive correlation exists between leptin and BMI as well as between leptin and testosterone in women with PCOS. These results may suggest that the feedback system in the interaction between leptin and NPY is disturbed in PCOS.//////////////////
Neuropeptide Y regulates proliferation and apoptosis in granulosa cells in a follicular stage-dependent manner. Urata Y et al. (2020) The complex regulatory mechanism involved in ovarian follicular development is not completely understood. Neuronal neuropeptide Y (NPY) is involved in the regulation of feeding behavior, energy homeostasis, and reproduction behavior, while its function in ovarian follicular development is not clear. The objective of this study was to investigate if and how NPY regulates follicle development in the ovary. All experiments were performed using Sprague Dawley rats. To understand NPY expression pattern at different stages of follicular development, NPY content was assessed using immunohistochemistry in individual follicles. NPY and its receptors expression pattern were evaluated in granulosa cells isolated from preantral (PA), early antral (EA) and late antral follicles (LAF). The influence of NPY on granulosa cell proliferation and apoptosis were further assessed in vitro, using Ki67- and TUNEL-positivity assays. To investigate whether NPY induced-proliferation in EA granulosa cells is mediated through the activation of NPY receptor Y5 (NPY5R) and Mitogen-activated protein kinase (MEK) signal pathway, EA granulosa cells were treated with NPY5R antagonist (CGP71683) and MEK inhibitors (PD98059 and U0126), and Ki67-positive cells were assessed. NPY protein expression was follicular stage-dependent and cell type-specific. NPY signal intensity in EA was higher than those in PA and LAF. Antral granulosa cells showed the highest signal intensity compared to mural granulosa cells, cumulus cells and theca cells. Granulosa cells NPY protein content and mRNA abundance were higher in EA than in LAF. NPY receptor contents in granulosa cells were follicular stage-dependent. While NPY reduced apoptosis of EA granulosa cells, it increased the proliferation through NPY5R and MEK pathway. In contrast, in LAF granulosa cells, NPY reduced proliferation and increased the number of apoptotic cells, with no significant effects on PA granulosa cells. This study is the first to evaluate the intraovarian role of NPY in granulosa cells at various stage of follicular development. These results indicate that NPY regulates granulosa cells proliferation and apoptosis in a follicular stage-dependent and autocrine manner. NPY may play a role in pathogenesis of ovarian follicular disorders.//////////////////
Results of Pitzel et al. (1991) suggest that SP and NPY have a modulatory effect on ovarian function in pigs not only by their well known regulatory effects of blood supply, but also by a direct effect on ovarian steroidogenesis. Miyamoto et al. (1993) studied the direct effects of neuropeptide Y (NPY) on the release of progesterone and oxytocin from midluteal phase CL (days 8-12). In long-term experiments, luteal cells were preincubated from the start of the culture for 48 h with NPY. During the following 4 h the neuropeptide showed a dose-dependent stimulation of progesterone release, but there was no effect on oxytocin release. LH showed a synergistic effect with NPY on progesterone release. In short-term experiments, the peptide was most stimulatory to LH-supported progesterone release.
Barreca et al. (1998) reported that Neuropeptide Y stimulates E2 production in human granulosa cells.
Evidence for a potential role of neuropeptide Y in ovine corpus luteum function. Keator CS et al. Neuropeptide Y (NPY) is a neurohormone that is typically associated with food intake, but it has also been reported to affect the production of progesterone from luteal tissue in vitro. However, NPY has not been previously immunolocalized in the ovine ovary or in the corpus luteum (CL) of any species, and the effects of this neurohormone on luteal function in vivo are not known. Thus, we performed fluorescent immunohistochemistry (IHC) to localize NPY in the ovine ovary and used avidin-biotin immunocytochemistry (ICC) to further define the intracellular localization within follicles and the CL. We then infused NPY directly into the arterial supply of the autotransplanted ovaries of sheep to determine the in vivo effect of exogenous NPY on ovarian blood flow and on the luteal secretion rate of progesterone and oxytocin. Immunohistochemistry revealed that the NPY antigen was localized to cells within the follicles and CL, in the nerve fibers of the ovarian stroma, and in the vessels of the ovarian hilus. In the follicle, the NPY antigen was localized to nerves and vessels within the theca interna layer, and strong staining was observed in the granulosal cells of antral follicles. In the CL, NPY was localized in large luteal cells and in the vascular pericytes and/or endothelial cells of blood vessels, found dispersed throughout the gland and within the luteal capsule. In vivo incremental infusions of NPY at 1, 10, 100, and 1,000 ng/min, each for a 30-min period, into the arterial supply of the transplanted ovary of sheep bearing a CL 11 d of age increased (P
Expression regulated by
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Ovarian localization
ovarian neuron
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In immunocytochemical studies with bovine ovaries, NPY was found around blood vessels and non-vascular smooth muscle cells, in the stroma near preantral follicles, and in the theca externa of antral follicles (Hulshof et al. 1994).
In rats, NPY immunoreactivity was demonstrated by immunohistochemistry to be localized within nerve fibers supplying blood vessels and follicles. The increase in the NPY content could not be related to accumulation around specific ovarian structures (Jorgensen et al, 1991). Ferruz et al. (1992) suggest that the release of norepinephrine (NE) from ovarian sympathetic nerves is subjected to a dual modulatory influence provided by NE itself and NPY; and this regulatory effect is exerted via specific prejunctional receptors. Such NE/NPY actions are likely to regulate the availability of NE to its postsynaptic receptors during ovarian development and adult function.
Follicle stages
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Neuropeptide Y (NPY) was measured in tissue extracts from ovaries of rats treated with pregnant mare serum gonadotropin (PMSG) by Jorgensen et al. (1991). The extracted NPY-immunoreactive material was identical to synthetic human NPY with regard to size and hydrophobicity as evaluated by gel filtration and high performance liquid chromatography. The concentration of NPY was related to the estrous cycle and a maximum was observed in relation to the endogenous luteinizing hormone (LH) peak. Employing an in vitro set-up, NPY was unable to induce ovulation and did not increase the ovulation rate in LH-stimulated ovaries.
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment:Erickson et al. (1996) reported that mice deficient for NPY have normal food intake and body weight, and become hyperphagic following food deprivation. Mutant mice decrease their food intake and lose weight, initially to a greater extent than controls, when treated with recombinant leptin.