A newUCLA and University of Utah study found how a hormone called hepcidin regulatesthe iron uptake from the diet and its distribution in the body. Thestudy may help develop future treatments for chronic anemia and for diseases ofiron overload, such as hemochromatosis.
Published online in the journal Science thisweek, researchers discovered that the hormone hepcidin controls ferroportin, aniron-transporting molecule on the surface of specific cells that containiron. Hepcidin signals ferroportin notto release iron into the blood stream.
Researchers realized that if there isn'tenough hepcidin to regulate ferroportin, too much iron is taken up from thedigestive system into the body, which can lead to hemochromatosis, a majorgenetic disorder affecting about a million people in the United States.
"For the first time we understand whathappens in the disease hemochromatosis," said Dr. Tomas Ganz, Ph.D., M.D., oneof the study's principal investigators and professor of medicine and pathologyat the David Geffen School of Medicine at UCLA. "We knew that ferroportin isnecessary to help release iron into the bloodstream, but didn't know thathepcidin directly regulates this activity."
Ganz adds that too much hepcidin present in the body --which can occur in patients with infections or with inflammatory diseases suchas rheumatoid arthritis or inflammatory bowel disease -- often results in notenough iron released into the blood stream causing chronic anemia.
"We have defined how the hormone hepcidinregulates the accumulation of iron by the body," says Jerry Kaplan, Ph.D.,one of the study's principal authors and a professor of pathology and assistantvice president for basic science at the University of Utah Health SciencesCenter. "This has implications for understanding both diseases that arecaused by not enough iron and diseases that are caused by too much iron."
In a cell culture, researchers added hepcidin to cells andfound that hepcidin attaches to ferroportin and causes ferroportin to be swallowedand destroyed by the cells. Withoutferroportin on the surface to release the iron, the mineral remains trappedinside the cell.
"Our findings may lead to new interventions for specificdiseases," said Dr. Elizabeta Nemeth, the study's first author and assistantresearch professor, Division of Pulmonary and Critical Care Medicine, DavidGeffen School of Medicine at UCLA."Our next step will be to look more closely at molecular interactions ofhepcidin and ferroportin in order to be able to develop treatment drugs."
Nemeth says that a form of hepcidin may be developed thatpeople with hemochromatosis could inject to help reduce the amount of irontaken up by the body – similar to the use of insulin to control the amount ofsugar in the body. For patients withanemia associated with too much hepcidin, Ganz adds that development of drugsto block hepcidin from binding to ferroportin might help release more iron intothe body.
Hemochromatosis is the most common genetic disease in theUnited States according to the Centers for Disease Control. One in 100-200people have a double mutation of a gene that puts them at risk for developinghemochromatosis, which causes an accumulation of excess iron in bodytissues. Anemia of chronic disease issecond only to iron-deficiency as a cause of anemia worldwide.
The National Institutes of Health funded the study. Other authors include: Marie S. Tuttle,Julie Powelson, Michael B. Vaughn and Diane McVey Ward from the Department ofPathology, School of Medicine, University of Utah; and Adriana Donovan,Department of Hematology, Children's Hospital, Boston, MA.