Beat it

Beat it

Height hormone offers target for fighting cancer and diabetes


An international team - including scientists from the University of Queensland in Australia - has discovered that a hormone that controls how tall we grow could be used to treat diseases like cancer and diabetes.
Led by Mike Waters, a professor in the Institute for Molecular Bioscience at the University of Queensland, the researchers report their findings in the journal Science.
"People without growth hormone receptor don't die from cancer or diabetes, making it an ideal drug target," says Prof. Waters.
However, he goes on to explain that we do not know enough about how growth hormone works to be able to design drugs to fight these diseases.
The hormone acts through its receptor - a unique protein on the surface of cells that binds uniquely to a hormone and allows it to send signals into cells.
The team thought if they could discover more about how the hormone interacts with its receptor - for instance which part of the molecule switches the receptor on and off - then they might uncover a useful target for designing drugs to fight diseases like cancer and diabetes.
This hunch did not arise suddenly. Prof. Waters has been studying growth hormone for 45 years. He originally cloned the receptor with leading global biotech Genentech.
"We've now figured out how growth hormone turns on its receptor at the molecular level," he explains, "and so have a clear idea of which part of the molecule to target to design drugs to combat these diseases."
Discovery has implications for other diseases
Lead author Dr. Andrew Brooks says the impact of their study goes further than cancer and diabetes:
"Growth hormone receptor is one of a group of proteins known as cytokine receptors, which are important targets for therapeutics for a range of disorders, including inflammatory bowel disease, blood disorders, osteoporosis and obesity."
He says that a better understanding of how the growth hormone receptor works will also give clues about how receptors for other cytokines work, which should help drug developers make treatments for many diseases.
For the study, the team used a combination of crystal structures, cell biology experiments, biophysical measurements, and dynamic models of how the receptor actually transmits the information bound in the hormone molecule.
The results suggest that the receptor remains in a dormant state that relies on two component molecules inhibiting each other. But when growth hormone comes along and binds to the receptor, it causes a structural change that "wakes up" the two components so they activate each other and trigger the cellular response to the hormone.
This mutual inhibition and activation model may also be how other similar cytokine receptors work, conclude the researchers.
Funds from the Australian Cancer Research Foundation, the National Health and Medical Research Council and the Australian Research Council helped finance the study.
In January 2011, Medical News Today learned how a compound that acts like an "un-growth" hormone can reverse some of the signs of aging.
The research team, which included a Saint Louis University physician, found that the compound, known as MZ-5-156, which acts in the opposite way to growth hormone, inhibited several human cancers, including prostate, breast, brain and lung cancers. The said the discovery may be counter-intuitive to some older adults who take growth hormone, thinking it will revitalize them.

Written by Catharine Paddock PhD