To view this page ensure that Adobe Flash Player version 11.1.0 or greater is installed.
After an erythropoietic stimulation such as hemorrhage, the levels of hormone erythropoietin (EPO) increase in circulation. EPO stimulates erythroblasts, the precursors of red blood cells in the
bone marrow, to secrete the hormone erythroferrone (ERFE). ERFE suppresses hepcidin production in the liver, which in turn results in greater iron availability for new red-blood-cell synthesis.
Illustration: Courtesy of Dr. Leon Kautz
Scientists at UCLA have discovered a new hormone, erythroferrone,
which regulates the supply of iron needed for the production of red
blood cells. Using a mouse model, researchers found that erythroferrone
is made by red-blood-cell progenitors in the bone marrow in order to
match iron supply with the demands of red-blood-cell production.
Erythroferrone is greatly increased when red-blood-cell production
is stimulated, such as after bleeding or in response to anemia. The
erythroferrone hormone acts by regulating the main iron hormone,
hepcidin, which controls the absorption of iron from food and
the distribution of iron in the body. Increased erythroferrone
suppresses hepcidin and allows more iron to be made available for
“If there is too-little iron, it causes anemia. If there is too-much
iron, the iron overload accumulates in the liver and organs, where
it is toxic and causes damage,” says Tomas Ganz, MD ’78 (RES ’81,
FEL ’83), PhD, professor of medicine and pathology. “Modulating
the activity of erythroferrone could be a viable strategy for the
treatment of iron disorders of both overabundance and scarcity.”
Researchers first focused on what happens in the bone marrow
after hemorrhage. From there, they focused on a specific protein
that was secreted into the blood. This protein attracted their
attention because it belonged to a family of proteins involved in
cell-to-cell communication. Using recombinant-DNA technology,
they showed that the hormone suppressed the production of
hepcidin and demonstrated the effect it had on iron metabolism.
The team foresees that the discovery could help people with a
common congenital blood disorder called Cooley’s anemia, also
known as thalassemia, which causes excessive destruction of red
blood cells and of their progenitors in the bone marrow. Many
of these patients require regular blood transfusions throughout
their lives. Most iron overload is attributed to the iron content of
transfused blood; however, even patients who are rarely, or never,
transfused can also develop iron overload.
“Overproduction of erythroferrone may be a major cause of
iron overload in untransfused patients and may contribute to
iron overload in transfused patients,” says Elizabeta Nemeth,
PhD, co-director of the UCLA Center for Iron Disorders. “The
identification of erythroferrone can potentially allow researchers
and drug developers to target the hormone for a specific treatment
to prevent iron overload in Cooley’s anemia.”
The discovery could also lead to treatments for other common
anemia-related conditions associated with chronic kidney disease,
rheumatologic disorders and other inf lammatory diseases.
In these conditions, iron is “locked up” by the effect of the
hormone hepcidin, whose levels are increased by inflammation.
Erythroferrone, or drugs acting like it, could suppress hepcidin
and make more iron available for red-blood-cell production. The
next stage of research is to understand the role of the new hormone
in various blood diseases and study the molecular mechanisms
through which erythroferrone regulates hepcidin.
“Identiﬁcation of erythroferrone as an erythroid regulator of iron metabolism,”
Nature Genetics, July 2014