Hormone crucial for skeletons

Researchers at the University of Otago, Christchurch have broken new scientific ground with discoveries regarding a previously little understood heart hormone, showing how it is crucial for bone development and growth after birth.

Working with other scientists in the USA, Professor Eric Espiner and Dr Tim Prickett are leading world research attempts to unravel questions about the heart hormone C- type Natriuretic Peptide (CNP) which have puzzled medical scientists since the hormone’s discovery in 1990.

Professor Espiner and colleagues within the internationally recognised Christchurch Cardioendocrine Research Group have shown for the first time that CNP, previously thought to regulate blood flow to tissues, also acts as a vital signal for skeletal growth at crucial stages in foetal and childhood development.

"This is a major advance in our understanding of how the skeleton develops in humans and could greatly assist in the early diagnosis and treatment world-wide of growth disorders in thousands of children, and those with rare bone disorders," explains Professor Espiner.

"After years of analysis we’ve demonstrated that the heart hormone CNP is produced at high levels in the foetus, and during rapid bone development at birth, with levels then slowly falling as growth rate slows. Then there’s another surge in CNP around puberty when there’s a new growth spurt and skeletal development."

The key to these findings has been the development of a specific test or assay to measure indicative levels of CNP in the blood. This has been achieved because over the last 25 years the Christchurch Cardioendocrine Research Group has developed internationally recognised expertise in designing complex tests for other closely related heart hormones, ANP and BNP.

Scientists Dr Tim Prickett and Associate Professor Tim Yandle developed the assay that has been the key to unlocking understanding of how CNP works in the body. Internationally no other research group has achieved this, although many have tried.

"Previously the hormone was only able to be measured in minute quantities in heart tissues and small blood vessels," Dr Prickett says. "But we’ve managed to develop a sensitive blood test for an inactive part of the hormone that reflects and magnifies the hormone’s activity in tissues.

There are many positives which flow on from this development says Professor Espiner.

"We’ve shown that measurements of the CNP hormone clearly correlate with growth rates in humans; when it’s high, growth rates and skeletal development are intense and rapid, when it is lower growth rates are reduced. " Levels are reduced by cortisone-like drugs.

"This finding is likely to have other useful clinical applications such as monitoring the use of powerful steroid drugs (and other medications) which may have a negative effect on bone growth in children. Early detection of such adverse effects should allow other treatment options to be considered."

The Christchurch Cardioendocrine Research Group has also made other recent discoveries regarding CNP and foetal health. Working with Professor Jane Harding at the University of Auckland, and Associate Professor Graham Barrell at Lincoln University, the group has found that CNP production is greatly increased in the foetus, and is also produced by the placenta.

Another study has proved that restricting food supply to pregnant sheep reduces the foetal CNP level, but increases the hormone in the mother. Similar changes occur in women who suffer from the potentially dangerous condition pregnancy toxaemia, suggesting that measuring CNP could be useful to detect stress in the unborn child.

Professor Espiner says this series of results show how new and unexpected roles for hormones may arise from heart research and illuminate other biomedical fields.

These unique contributions to this research are being recognised by a special invitation to the Group to present its findings at the forthcoming annual meeting of the British Society for Endocrinology in April.

(Source: Annual Meeting of the British Society for Endocrinology: University of Otago: February 2008)