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T Prickett, Medicine, University of Otago, Christchurch, Christchurch, 8140, New Zealand
G Barrell, Agriculture & Life Sciences Division, Lincoln University, Canterbury, New Zealand
M Wellby, Agriculture & Life Sciences Division, Lincoln University, Canterbury, New Zealand
T Yandle, Medicine, University of Otago, Christchurch, Christchurch, 8140, New Zealand
A Richards, Medicine, University of Otago, Christchurch, Christchurch, 8140, New Zealand
E Espiner, Medicine, University of Otago, Christchurch, Christchurch, New Zealand

Correspondence: Timothy Prickett, Email: tim.prickett{at}otago.ac.nz

Abstract

Although C-type natriuretic peptide (CNP) is crucial to postnatal endochondral growth, roles for the hormone in pubertal bone growth and the physiological effects of sex steroid substitution on CNP synthesis are not known. Using a plasma marker of CNP tissue synthesis (aminoterminal proCNP, NTproCNP), we have studied the effect of exogenous oestrogen (E2) or testosterone (T) on plasma CNP forms and bone alkaline phosphatase (bALP) in prepubertal lambs. Responses to E2 in non-cycling adult ewes were also studied. In 15 week old intact ewe lambs, E2 promptly increased plasma NTproCNP and CNP (p<0.001) to peak on day 2, and bALP (p<0.001 peaking on day 7) whereas no significant stimulation in response to T was observed in male lambs. Linear bone growth and live weight were unaffected. In adult anoestrous ewes, basal concentrations of CNP forms and bALP were lower than in ewe lambs, in keeping with skeletal maturity, but adults responded similarly to E2. Prompt and sustained increases in NTproCNP and CNP, and a later 3-fold rise in bALP (all p<0.001) were induced by E2. Possible contributions to these increases in plasma CNP forms by reproductive tissues (a known site of E2-induced CNP expression) were excluded by showing similar E2-induced CNP responses in adult ewes after surgical removal of reproductive tissues.

These results are the first to show that E2 stimulates plasma CNP forms and bALP in lambs and adult sheep and raise the possibility that CNP also participates in bone formation in the mature skeleton.