Olney Robert C
Division of Pediatric Endocrinology, Nemours Children's Clinic, 807 Children's Way, Jacksonville, FL 32207, USA.
Growth Horm IGF Res. 2006 Jul;16 Suppl A:S6-14. doi: 10.1016/j.ghir.2006.03.016. Epub 2006 May 22.
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.
C型利钠肽（CNP）通过其受体利钠肽受体-B（NPR-B）发挥作用，在线性生长中起关键作用。CNP基因敲除小鼠和NPR-B基因敲除小鼠均表现为侏儒症，而过度表达CNP的转基因小鼠则过度生长。CNP对生长板软骨细胞具有直接调节作用，主要作用是促进终末分化和肥大。在人类中，纯合子NPR-B突变是导致马罗泰克斯型肢端中胚层发育不良（AMDM）的原因，这是一种严重的不成比例侏儒症。一名AMDM患者和NPR-B基因敲除小鼠的胰岛素样生长因子I（IGF-I）水平均较低，提示这些调节系统之间存在相互作用。NPR-B突变的杂合子携带者身高也降低，但无其他异常。因此，杂合子NPR-B突变是“特发性”身材矮小的另一个原因。直到最近才发现CNP-NPR-B系统是人类生长的重要调节因子，该系统的异常具有临床意义。需要开展大量工作以进一步了解这种人类生长调节的新范式。
