Scientists Find Key to Iron Disorders

THURSDAY, Oct. 28, 2004 (HealthDayNews) -- For years, experts have known that a hormone called hepcidin regulates the amount of iron circulating in the bloodstream, but the way in which it interacts with cells has remained a mystery.

Now, that mystery has been solved.

The finding could lead to new treatments for anemia and hemochromatosis, two blood-iron disorders that affect millions of Americans.

"We know who the players are now," explained lead researcher Dr. Tomas Ganz, a professor of medicine at the University of California, Los Angeles, School of Medicine. He said the new research "outlines how all the pieces fit together."

A report on the cellular process appears in the Oct. 28 online issue of Science.

Iron is crucial to good health, but chronic ailments can alter the amount of iron in the blood: When there's too little, anemia is the result; when there's too much, a genetic disorder known as hemochromatosis wreaks havoc on critical organs.

"It's basically a situation where you absorb too much iron from your diet," Ganz said of hemochromatosis. "You end up depositing that excess iron, first into the liver, where it causes tissue damage. The liver eventually gets destroyed, and some people can get liver cancer as well. It can be very serious." Ganz estimated that up to 2 percent of individuals of Northern European descent carry the gene for hemochromatosis.

Scientists have long understood that hepcidin plays a big role in both blood disorders. In the latest study, Ganz and his colleagues examined the activity of cells under the microscope to determine the mechanism behind that relationship.

"We discovered that a receptor on the surface of cells, called ferroportin, is the receptor for hepcidin," Ganz said.

"But it's more than a receptor -- it's the channel through which iron exits from the cell," he added. Excess hepcidin seems to shut down those channels, keeping iron locked within cells.

"When this happens in the intestine, it stops the ability of the body to take up iron from the diet, and in other parts of body it stops the release of iron from various tissues," he said.

Unfortunately, bone marrow requires a steady supply of iron to make new red blood cells, and when excess hepcidin cuts off that supply, anemia is the result.

On the other hand, a shortage of hepcidin appears to increase the activity of ferroportin receptors. This causes them to take in too much iron from the diet, exactly the situation seen in patients with hemochromatosis.

This new understanding may open the door to novel treatments, Ganz said.

"We can start developing [drugs] that are similar to hepcidin, so we can treat conditions where the hormone is low," Ganz said. "Or we can find molecules that oppose the action of hepcidin -- those could be used to treat anemia seen in chronic disease, where the hormone is too high."

While the development of those drugs might take years, Ganz said the findings have at last brought experts to a point "where the whole system fits together."

More information

For more on hemochromatosis, go to the National Institutes of Health.