title: Pharmacodynamic responses of plasma and tissue C-type natriuretic peptide to GH: correlation with linear growth in GH-deficient rats.
abstract: Studies from genetic modification and spontaneous mutations show that C-type natriuretic peptide (CNP) signalling plays an essential part in postnatal endochondral growth, but measurement of CNP proteins and changes in their abundance in tissues and plasma during normal growth has not been reported. Using rodent pups with GH deficiency, we now describe the pharmacodynamic response of CNP and rat amino-terminal proCNP (NTproCNP) in plasma and tissues, and relate these to changes in linear growth (nose-tail length, tibial length and tibial growth plate width) during the course of 1 week of GH or saline (control) administration. Compared with saline, significant increases in plasma and tissue CNP forms were observed after 24 h in GH-treated pups and before any detectable change in linear growth. Whereas CNP abundance was increased in most tissues (muscle, heart and liver) by GH, enrichment was the greatest in extracts from growth plates and kidney. Plasma and tissue concentrations in GH-treated pups were sustained or further increased at 1 week when strong positive associations were found between plasma NTproCNP and linear growth or tissue concentrations. High content of NTproCNP in kidney tissue strongly correlated with plasma concentrations, which is consistent with previous data showing renal extraction of the peptide. In showing a prompt and significant increase in CNP in tissues driving normal endochondral growth, these findings provide further rationale for CNP agonists in the treatment of growth disorders resistant to current therapies and support the use of CNP concentrations as biomarkers of linear growth.
authors.affiliation: Department of Medicine, University of Otago, Christchurch, PO Box 4345, Christchurch 8140, New Zealand. tim.prickett@otago.ac.nz
authors.forename: T C R
authors.initials: TC
authors.lastname: Prickett
authors.forename: J C
authors.initials: JC
authors.lastname: Bothwell
authors.forename: T G
authors.initials: TG
authors.lastname: Yandle
authors.forename: A M
authors.initials: AM
authors.lastname: Richards
authors.forename: E A
authors.initials: EA
authors.lastname: Espiner
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001837:Body Weights and Measures; D001846:Bone Development / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004393:Dwarfism, Pituitary / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D013006:Growth Hormone / Q000235:genetics; D006132:Growth Plate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020249:Hormone Replacement Therapy; D019382:Human Growth Hormone / Q000235:genetics / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000097:blood / Q000378:metabolism*; D009928:Organ Specificity; D011498:Protein Precursors / Q000097:blood / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D015415:Biomarkers; D011498:Protein Precursors; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D020098:Natriuretic Peptide, C-Type; D013006:Growth Hormone