C-type natriuretic peptide in growth: A new paradigm

C-type natriuretic peptide (CNP), acting through its receptor, natriuretic peptide receptor-B (NPR-B), plays a critical role in linear growth. Knockout mice for CNP and NPR-B are dwarfed, and transgenic mice overexpressing CNP are overgrown. CNP has a direct regulatory effect on growth plate chondrocytes, acting primarily to promote terminal differentiation and hypertrophy. In humans, homozygous NPR-B mutations are the cause of acromesomelic dysplasia, Maroteaux type (AMDM), a severe form of disproportionate dwarfism. A patient with AMDM and the NPR-B knockout mouse both have low insulin-like growth factor I (IGF-I) levels, suggesting an interaction between these regulatory systems. Heterozygous carriers of NPR-B mutations also have reduced stature, but no other abnormalities. Hence, heterozygous NPR-B mutations are another cause of “idiopathic” short stature. The CNP–NPR-B system has only recently been found to be an important regulator of human growth, and abnormalities in this system have clinical implications. Considerable work is needed to further understand this new paradigm of human growth regulation.