Renal effects of neuropeptide Y

Bischoff, Angela; Michel, Martin C.

doi:10.1007/s004240050538

Cited by 62 publications

(57 citation statements)

References 94 publications

(202 reference statements)

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Section: Neuroendocrine Control Of Bone and Fatmentioning

confidence: 99%

“…In addition to effects in the brain, the NPY system regulates energy homeostasis via actions on Y1 and Y2 receptors in peripheral tissues such as the liver and adipocytes [11,98]. Besides effects on energy balance, the NPY system regulates numerous processes such as fluid balance [99] resorption.In addition to estrogen effects on bone, androgens are important regulators of bone cell activity and bone mass in both humans and mice [30]. ARs are found in both osteoblasts and osteoclasts; however, they are primarily expressed in osteoblasts and to a greater degree in cortical than cancellous bone [31].…”

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confidence: 99%

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Neuropeptide Y and sex hormone interactions in humoral and neuronal regulation of bone and fat

Zengin

Zhang

Herzog

et al. 2010

Trends in Endocrinology & Metabolism

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The hypothalamus regulates the skeleton and adipose tissue via endocrine mechanisms. Changes in sex steroid levels in menopause and aging are central to the associated changes in bone mass and adiposity. Whereas many of these effects occur via direct actions on osteoblasts or adipocytes, sex hormones can also mediate effects on bone and adipose tissue via interaction with neuronal pathways. A key hypothalamic regulator of bone and adipose tissue is neuropeptide Y (NPY), which coordinately influences these tissues via effects on neuroendocrine and sympathetic nervous output. Better understanding of the interaction between NPY and sex steroids in regulating skeletal and energy homeostasis could lead to more effective treatments for osteoporosis and obesity. Neuroendocrine control of bone and fatOsteoporosis and excess central adiposity, increasingly prevalent in ageing populations, increase the risk of fractures and diseases such as type-2 diabetes mellitus, and adversely affect both quality of life and survival. The regulation of bone and adipose tissue mass has traditionally been studied independently, but osteoblasts and adipocytes are derived from the same mesenchymal precursor cells, and recent findings that the bone-or fat-derived hormones, osteocalcin and leptin, have significant effects on energy homeostasis and bone [1], respectively, now suggest that bone and adipose tissue share common regulatory pathways. The hypothalamus acts as a pivotal regulator of homeostasis in bone and adipose tissue via regulation of hypothalamopituitary axes. For instance, activation of the hypothalamo-pituitary-adrenal axis, or inhibition of the hypothalamo-pituitary-somatotropic or -gonadotropic axes (as in stress or negative energy balance), can affect circulating concentrations of cortisol, insulin like growth factor-1 (IGF-1) and sex steroids that inhibit bone formation while promoting conservation of fat mass, particularly central adiposity 2, 3 and 4. Sex hormones -a major focus of this review -influence bone and fat via direct actions on osteoblasts or adipocytes 2, 3, 5, 6, 7 and 8. Recently, however, it has been recognized that sex hormones can influence these tissues via the neuropeptide Y (NPY) system (Box 1) 9, 10, 11 and 12, that also regulates bone and adipocyte homeostasis via actions in the hypothalamus and peripheral tissues 9, 13 and 14. In this review we examine the role of sex hormones in skeletal and energy homeostasis, with particular focus on their interaction with NPY. Whereas research into the isolated effects of sex hormones or the NPY system on bone and adipose tissue homeostasis has led to identification of potential novel drug targets for the treatment of osteoporosis or central obesity, emerging research into the interaction of these systems could pave the way for even better treatments for these conditions, particularly in the context of reduced circulating concentrations of sex hormones, as in menopause or ageing in women and in men. Zenging et al.: Trends in Endocrinology & Metabolism, 2(7): 4...

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Section: Neuroendocrine Control Of Bone and Fatmentioning

confidence: 99%

mentioning

confidence: 99%

Neuropeptide Y and sex hormone interactions in humoral and neuronal regulation of bone and fat

Zengin

Zhang

Herzog

et al. 2010

Trends in Endocrinology & Metabolism

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“…Both in vivo and in vitro studies have demonstrated that NPY inhibits glucose-stimulated insulin secretion (6,7). NPY has also been shown to regulate renal blood flow (8). Stimulation of the NPY receptors in the kidney, using active agonists, may decrease glomerular filtration rate, aldosterone concentration, and plasma renin activity, but increase sodium excretion in the kidney (9).…”

Section: Introductionmentioning

confidence: 99%

Distribution of neuropeptide Y Leu7Pro polymorphism in patients with type 1 diabetes and diabetic nephropathy among Swedish and American populations

Ma¹,

Nordman²,

Möllsten

et al. 2007

European Journal of Endocrinology

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Objective: The distribution of Leu7Pro polymorphism in the neuropeptide Y gene shows a geographical north to south gradient of decreasing frequency, suggesting that it may be a population-specific causal variant. This polymorphism is found to be associated with diabetic nephropathy (DN) and coronary heart disease in Finnish women with type 1 diabetes (T1D). The present study aims to evaluate the susceptibility of this polymorphism to the development of DN in two different populations. Design: One sample set consists of 174 (females 98 and males 76) Swedish T1D patients with DN and 249 (females 132 and males 117) patients without DN. Another sample set includes 597 (females 356 and males 241) American T1D patients without DN and 577 (females 264 and males 313) patients with DN, who were descents of European Caucasians and were from the Genetics of Kidneys in Diabetes (GoKinD) Study. Methods: Genotyping of Leu7Pro polymorphism was performed by dynamic allele-specific hybridization. Results: The C allele frequencies of Leu7Pro polymorphism in T1D patients between Swedish and American GoKinD populations were significantly different (6.3 vs 4.0%; PZ0.006). Particularly, the C allele frequency in Swedish female T1D patients with DN was significantly higher in comparison with T1D patients without DN (10.2 vs 4.2%; PZ0.011, ORZ2.614, 95% confidence intervals: 1.249-5.467). No significant association of this polymorphism with DN was observed in Swedish male T1D patients and the patients from GoKinD. Conclusions:The present study provides further evidence that Leu7Pro polymorphism confers the susceptibility to the development of DN in Swedish female T1D patients.European Journal of Endocrinology 157 641-645

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“…27 From this NPY receptor distribution, a regulatory role of NPY in renal perfusion and tubular function can be suggested, in accordance with scarce experimental data on the functional renal effects of NPY. 28 Moreover, as we and others provide in vitro evidence for Y1 receptor expression in the precursor cells of RCCs and nephroblastomas, i.e., in tubules and nephrogenic blastema, 27 respectively, it can be assumed that the Y1 receptors in renal tumors are probably not expressed de novo as opposed to the NPY receptors in pheochromocytomas and paragangliomas. 10 Since nephroblastomas express Y1 as well as Y2, one may speculate that a switch in NPY receptor subtype expression occurs in embryonal tumor cells.…”

Section: Discussionmentioning

confidence: 80%

“…While it is possible that binding of NPY to vascular receptors could result in vasoconstriction, 28 tumor ischemia and necrosis, potential direct effects via tumor cell receptors on cell metabolism and proliferation are unclear. It was shown that NPY can inhibit the growth of tumor cell lines under certain conditions 8 and stimulate it in others.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y receptors in renal cell carcinomas and nephroblastomas

Körner

Waser

Reubi

2005

Intl Journal of Cancer

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Numerous peptide receptors are overexpressed in human cancer, permitting in vivo tumor targeting. Among such receptors, those for the neurotransmitter neuropeptide Y (NPY) are overexpressed in various tumors. Since NPY can play a role in the kidney, NPY receptor expression and/or endogenous production of peptides of the NPY family (NPY, PYY, PP) were evaluated in 40 renal cell carcinomas (RCCs) and 18 nephroblastomas. NPY receptor protein expression was investigated by in vitro autoradiography using 125 I-labeled PYY in competition with NPY receptor subtype-selective analogs. NPY, PYY and PP production was assessed immunohistochemically. Fifty-six percent of RCCs expressed the Y1 receptor subtype in moderate density, and 80% of nephroblastomas expressed Y1 and Y2 subtypes in moderate to high density. Y1 was also highly expressed in intratumoral blood vessels. In selected cases, NPY was observed in nerve fibers in close association with intratumoral blood vessels and in the vicinity of tumor cells, while no PYY or PP was detected immunohistochemically in these sites. NPY receptors on renal tumor cells and tumor blood vessels may therefore be the molecular targets of endogenous NPY released by intratumoral nerve fibers. With regard to clinical applications, NPY receptors may act as in vivo targets for receptor-directed therapy of RCCs and nephroblastomas for which alternative therapeutic approaches are still required. ' 2005 Wiley-Liss, Inc.Key words: NPY receptor; renal cell carcinoma; nephroblastoma; receptor autoradiography Peptide hormone receptors are overexpressed in a wide variety of human tumors.1 Like other cell surface molecules, these receptors become increasingly important for clinical applications. In particular, they allow receptor-targeted tumor imaging and therapy with corresponding peptide hormone analogs. For instance, scintigraphy using the somatostatin analog Octreoscan is highly sensitive at detecting gastroenteropancreatic neuroendocrine tumors which express somatostatin receptors in high amounts.2,3 Moreover, targeted radiotherapy of these tumors with 90 Y-or 177 Lu-labeled somatostatin analogs is also promising. 4,5 Another peptide hormone receptor family with a potential future role in this field is the NPY receptor family. It belongs to the G protein-coupled receptor superfamily and comprises various subtypes. Subtypes Y1, Y2, Y4 and Y5 are expressed in humans. 6 They are present mainly in the central and peripheral nervous systems as well as other tissues, such as the cardiovascular system. Their physiologic ligands are the neurotransmitter NPY and the 2 hormones PYY and PP. Among many other sites, NPY has been localized to perivascular nerves in the human kidney. 7 NPY receptors may also play a role in human neoplasia. High incidence rates of subtypes Y1 and Y2 were found in tumors related to steroid hormone metabolism (adrenal cortical tumors, ovarian sex cord-stromal tumors, breast carcinomas), 8,9 in neuroendocrine tumors (pheochromocytomas and paragangliomas) 10

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Renal effects of neuropeptide Y

Cited by 62 publications

References 94 publications

Neuropeptide Y and sex hormone interactions in humoral and neuronal regulation of bone and fat

Neuropeptide Y and sex hormone interactions in humoral and neuronal regulation of bone and fat

Distribution of neuropeptide Y Leu7Pro polymorphism in patients with type 1 diabetes and diabetic nephropathy among Swedish and American populations

Neuropeptide Y receptors in renal cell carcinomas and nephroblastomas

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