Too much iron leads to iron overload and organ damage. Too little and an individual becomes anemic. And there are different causes for either condition.

But recently, University of Utah School of Medicine researchers have figured a way to tell whether the cause is related to how iron is exported from cells, and therefore chronic.

A hormone called hepcidin, made by the liver, is key to regulating iron balance. It binds to a receptor that transports iron, ferroportin, reducing how much is exported. That means if someone has a lot of the hormone, it doesn't transport the iron, and the result is anemia. If there's too little hepcidin, too much iron is exported from the cells and the individual has iron overload, according to senior author Jerry Kaplan, professor of pathology and assistant vice president for research at U. Health Sciences.

The researchers worked out precisely where the hormone binds, finding it's the same in all species, from fish to humans. Then they created an assay, Kaplan said.

Researchers from the U. and from UCLA made a synthetic version of that binding site on agarose beads to develop a quick and sensitive test called the hepcidin-binding domain (HBD) assay, to measure how much active hepcidin is in blood.

One of the authors, Diane M. Ward, said that the ferroportin molecule has a series of amino acids that can hook to plastics. By passing those beads through biologic fluid then through a radioactive hepcidin, they can tell how much hepcidin is in the fluid because when it binds to the receptor, the radioactive version will not stick.

The HBD assay readily determines variations in hepcidin levels caused by gene mutations known to affect those levels, as well as mutations in genes involved in iron metabolism, according to a release announcing the assay. And it can measure the hormone concentration in response to inflammation, so doctors could distinguish anemia and iron overload caused by hepcidin levels from those that have other causes.

Humans have one hepcidin molecule, while fish have many, but the receptor is identical. The hormone was first noted for antibacterial and antifungal activity, but it now appears its main role in the body is to regulate iron balance.

Researchers also found that hepcidin's binding ability decreases as temperatures drop below normal body temperature. Now they're wondering about the effects of low temperatures on iron metabolism and antibacterial activity. They found human hepcidin has both iron and bacteria-related activities, while in fish the two functions are separated.

They found that fish had separated the two functions, while hepcidin took care of both in humans, offering insights into the evolution of the hormone among vertebrates

The work started as an experiment by a researcher in Kaplan's lab, Ivana De Domenico, that Kaplan "never thought would work." A year later, they've figured out the evolution of the hormone and created a way to measure it. That assay, said Kaplan, can be used on any vertebrate.

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