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C-Type Natriuretic Peptide (CNP) and Postnatal Linear Growth

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Handbook of Growth and Growth Monitoring in Health and Disease

Abstract

C-type natriuretic peptide (CNP) is a member of a family of structurally related peptides, including atrial (ANP) and B-type (BNP) natriuretic peptides, best known for their cardiovascular actions. Surprisingly, recent evidence from rodents shows that CNP is essential for endochondral bone growth – blocking the CNP signaling pathway yields a dwarfed phenotype whereas overexpression leads to skeletal overgrowth. In humans, loss of function mutations in the CNP receptor gene (NPR-B) cause the profoundly dwarfed phenotype of acromesomelic dysplasia Maroteaux type. By contrast, overexpression of CNP, arising from balanced translocations involving chromosome 2, results in severe skeletal overgrowth as reported recently in three patients with marfanoid habitus. CNP is expressed in a broad range of tissues including bone, but the circulating concentration of CNP in blood is low, close to assay detection limits, due in part to its rapid degradation by clearance receptors and enzyme hydrolysis. However, a stable product of the CNP gene, amino-terminal proCNP (NTproCNP), is readily measurable in plasma and has been used to study the regulation of CNP secretion in vivo. Plasma NTproCNP is strongly correlated with skeletal growth and markers of bone formation in lambs and children throughout the growing period. In addition plasma levels of NTproCNP are rapidly suppressed by glucocorticoid treatment or caloric restriction (which reduce growth) and stimulated by anabolic hormones including GH, thyroid hormones, and estrogens. These and other recent findings support the view that the plasma concentration of NTproCNP, in reflecting growth plate cartilage activity, is a unique marker of linear growth which may assist in the diagnosis of growth disorders in humans.

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Abbreviations

ANP:

Atrial natriuretic peptide

BMP-2:

Bone morphogenetic protein 2

BMP-4:

Bone morphogenetic protein 4

BNP:

B-type natriuretic peptide

cGKII:

cGMP-dependent protein kinase II

CNP:

C-type natriuretic peptide

FGFR3:

Fibroblast growth factor receptor 3

GC:

Guanylate cyclase

GH:

Growth hormone

IGF-1:

Insulin-like growth factor 1

NPR-A:

Natriuretic peptide receptor type A

NPR-B:

Natriuretic peptide receptor type B

NPR-C:

Natriuretic peptide receptor type C

NTproCNP:

Aminoterminal pro C-type natriuretic peptide

proCNP:

C-type natriuretic peptide prohormone

TGFβ:

Transforming growth factor-beta

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Acknowledgments

The authors would like to gratefully acknowledge the contributions to this work by the following colleagues: Vicky Cameron, Brian Darlow, Mark Richards, Tim Yandle (University of Otago, New Zealand); Graham Barrell, Martin Wellby (Lincoln University, New Zealand); Bronwyn Dixon, Adrienne Lynn (Christchurch Hospital, New Zealand); Jane Harding (Liggins Institute, New Zealand); Rob Olney (Nemours Children’s Clinic, Pensacola, FL, USA); Mitch Geffner and Christina Southern Reh (Childrens Hospital Los Angeles, Keck School of Medicine of USC, Los Angeles, USA). This work was supported by grants from the Health Research Council of New Zealand, the Canterbury Medical Research Foundation and the Lotteries Board of New Zealand, the National Heart Foundation, and the New Zealand Child Health Research Foundation.

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  1. Department of Medicine, University of Otago, Christchurch, 8140, New Zealand

    Timothy C.R. Prickett

  2. Department of Medicine, University of Otago, Christchurch, 8140, New Zealand

    Eric A. Espiner

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  1. Timothy C.R. Prickett
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Correspondence to Timothy C.R. Prickett .

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  1. Dept. Nutrition & Dietetics, King's College, Stamford St. 150, London, SE1 9NH, United Kingdom

    Victor R. Preedy

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Prickett, T.C., Espiner, E.A. (2012). C-Type Natriuretic Peptide (CNP) and Postnatal Linear Growth. In: Preedy, V. (eds) Handbook of Growth and Growth Monitoring in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1795-9_166

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