Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


After a 40-year search, a hormone controlling iron metabolism in mammals is finally identified


Iron is vital for cells, because it catalyzes key enzyme reactions; it is also crucial for respiration, fixing atmospheric oxygen to hemoglobin in red blood cells. Iron deficiency can lead to severe anemia, with inadequate tissue oxygenation. An excess of iron is also toxic, as it facilitates the generation of free radicals that can attack the liver, heart and pancreas. This is the case in hereditary hemochromatosis, a genetic disorder which, in 80% of cases, is linked to a point mutation in the Hfe-1 gene, leading to excessive iron uptake by the intestinal tract. Hereditary hemochromatosis is very frequent in western countries, affecting one in 300 people. The body has no physiological mechanism for eliminating iron, and the only effective treatment for patients with hereditary hemochromatosis is bleeding, in some cases several times a week. These patients, and their doctors, are eagerly awaiting a breakthrough in our understanding of the mechanisms regulating iron metabolism, that might have therapeutic implications.

Dietary iron enters the body via cells known as enterocytes, that line the intestinal folds. Humoral signals are known to modulate how much iron these cells take up, according to the body`s internal stores. Yet, despite intense research over the last four decades, no-one had previously been able to identify these signals.

It is by chance that Gaël Nicolas, Sophie Vaulont and their coworkers came across such a signal while working on knock-out mice developed in their laboratory. The mice lacked a transcription factor known as USF2 (upstream stimulatory factor 2), thought to be involved in glucose metabolism. To their surprise, the team found that the mice had disorders similar to those of patients with hereditary hemochromatosis, namely premature ageing of the pancreas and liver, which take on an abnormal brown color - a sign of iron accumulation. Further tests indeed showed that the animals had a form of hemochromatosis. Intrigued, the team created a subtractive RNA bank in order to determine whether any other genes were abnormally expressed in their model. This was effectively the case. One abnormally expressed gene was found to correspond to a recently identified sequence of 25 amino acids found in members of an antimicrobial peptide family called the defensins. The peptide in question - hepcidin - is produced by the liver and secreted into the bloodstream. Hepcidin has a degree of antimicrobial activity, but Axel Kahn, Sophie Vaulont and their colleagues at Bichat Hospital in Paris believe that it acts essentially as a true hormone, inhibiting iron uptake by intestinal cells; they also believe that when hepcidin dysfunctions the body has no way of limiting iron absorption into the bloodstream.

To test this hypothesis, the team first checked that iron levels were normal in a transgenic mouse model, produced in another laboratory, that lacks USF2 but has an intact hepcidin gene. Then they went on to create transgenic mice whose livers overproduced hepcidin, expecting them to develop anemia. In the event, almost all the new-born animals were smaller than normal, had very pale skin and no hair, were profoundly anemic, and died within hours of birth - unless they received an injection of iron. (Some animals producing less hepcidin were less severely anemic and survived without treatment.)

This discovery opens up exciting therapeutic and diagnostic perspectives in diseases due to abnormal iron homeostasis. Therefore, a patent application has been filed by INSERM and the inventors. One short-term possibility is a diagnostic test based on serum hepcidin measurement. In the longer term, the development of hepcidin agonists and antagonists may well transform the treatment of these frequent and potentially severe disorders.

Nathalie Christophe | alphagalileo

More articles from Life Sciences:

nachricht ‘Farming’ bacteria to boost growth in the oceans
24.10.2016 | Max-Planck-Institut für marine Mikrobiologie

nachricht Calcium Induces Chronic Lung Infections
24.10.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Oasis of life in the ice-covered central Arctic

24.10.2016 | Earth Sciences

‘Farming’ bacteria to boost growth in the oceans

24.10.2016 | Life Sciences

Light-driven atomic rotations excite magnetic waves

24.10.2016 | Physics and Astronomy

More VideoLinks >>>