ABCs of Natriuretic Peptides: Growth

Abstract

Background: Although they are better known for their cardiovascular and antiproliferative effects, natriuretic peptides also have been found to produce skeletal overgrowth in transgenic rodents. This finding has unmasked a novel paracrine role in endochondral bone growth for this family of hormones. Genetic studies in which key components in the C-type natriuretic peptide (CNP) signaling pathway are disrupted or overexpressed and spontaneous mutations in the CNP receptor in humans indicate that CNP plays a crucial role in determining postnatal skeletal elongation. CNP appears to promote expansion within several areas of the growth plate, but its effects are most obvious in the hypertrophic zone. Since its actions are largely paracrine in nature, new approaches are needed to study CNP’s role in vivo. CNP itself degrades rapidly, but amino-terminal pro-CNP (NT pro-CNP) escapes rapid degradation and can be readily detected in plasma. Methodology: Studies have been made of changes in CNP synthesis in humans and sheep by measuring NT pro-CNP levels. Plasma NT pro-CNP levels are markedly elevated in newborns, but fall progressively as growth velocity declines in both children and lambs. In keeping with these growth-related changes, CNP levels are inhibited by glucocorticoids and malnutrition in lambs and are stimulated by growth hormone and testosterone in adolescent boys. Further, levels fall abruptly in children receiving growth-suppressing chemotherapy regimens. Conclusions: Plasma NT pro-CNP levels may be an indicator of CNP synthesis within skeletal tissues and provide a much needed biomarker of linear growth, with applications for diagnosis and management of growth disorders.