Endocrine Abstracts

CNP belongs to a family of peptides best known for their role in blood pressure regulation and cardiac remodeling. However CNP differs from the cardiac hormones (ANP and BNP) in showing more diverse expression and low circulating plasma concentrations. Genetic studies, as well as showing cardioprotective roles for all three hormones, have revealed a critical role for CNP in promoting linear growth in both rodents and humans. Finding that the aminoterminal bio-inactive fragment of proCNP (NTproCNP), readily measurable in plasma, reflects CNP synthesis has further added to our understanding of CNP’s paracrine role in vivo. Thus plasma NTproCNP concentration correlates strongly with linear growth velocity in neonates, children and adolescents, as well as during normal growth and during interventions affecting growth velocity in lambs. Collectively these findings support the view that CNP is a driver of growth plate expansion throughout post natal growth.

Skeletal actions of CNP unrelated to endochondral growth are also likely. Studies on the effects of sex steroids in prepubertal lambs show that oestrogens, but not testosterone, promptly increase plasma CNP forms and bone specific alkaline phosphatase yet growth velocity is unaffected. Since similar responses to oestrogen were observed in adult ewes, the findings suggest that CNP also participates in bone renewal in the adult skeleton.

Measurements of NTproCNP have revealed new roles for the hormone in fetal-maternal welfare where CNP is regulated independently in the ovine fetus. Reciprocal responses to maternal undernutrition (fall in fetal plasma CNP forms as maternal levels increase) suggest that the utero-placental unit’s production of CNP is responsive to substrate deficiency, and that maternal NTproCNP concentrations may be a marker of utero-placental nutrient supply.

In summary, genetic manipulations and new methods measuring changes in CNP synthesis in vivo, in opening up new vistas continue to illuminate CNP’s role in health and disease.