| المجلد 4 ,
العدد 8
, ذو الحجة 1428 - كانون الثاني (يناير) 2008 |
| |
Hepcidin: an Iron Regulatory Hormone
and a New Laboratory Test for Iron Metabolism
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| الهيبسيدين: هرمون منظم للحديد واختبار مخبري لاستقلاب الحديد |
| Yousif Y. Bilto |
| د. يوسف بيلتو |
| University of Jordan |
| Background |
| Human hepcidin, a 25–amino acid peptide made by hepatocytes, secreted in the plasma and excreted in the urine, was first purified from human blood and urine as an antimicrobial peptide that was found to be predominantly expressed in the liver. Hepcidin is now believed to be the long-sought iron-regulatory hormone and a new mediator of innate immunity. The synthesis of hepcidin is greatly stimulated by inflammation or by iron overload and suppressed by iron deficiency, anemia or hypoxia. Hepcidin deficiency causes severe iron overload and over-production of hepcidin results in iron-deficiency anemia. Hepcidin is decreased in hemochromatosis and thalassemia major patients and increased in anemia of chronic disease patients suggesting that the relationship between body iron status and hepcidin is altered in these conditions. Increased production of hepcidin in anemia of chronic disease may account for the well known feature of this anemic condition, that is sequestration of iron in macrophages. These and other evidences indicate that hepcidin is the predominant negative regulator of iron absorption in the small intestine, iron release from macrophages, and iron transport across the placenta. The most important cellular targets for hepcidin seems to be the villus enterocyte, the reticuloendothelial macrophage, and the hepatocyte. However, hepcidin was also shown to co-operate with pro- and anti-inflammatory cytokines in causing a diversion of iron traffic leading to iron retention in macrophages and an iron–restricted erythropoiesis. This short communication discusses the current understanding of iron metabolism and the proposed role for hepcidin in normal iron homeostasis. |
| Current understanding of iron homeostasis: |
| Iron homeostasis is dependent upon tightly linking body iron requirements with intestinal iron absorption. Several factors have been found to influence the rate of iron absorption including: 1) marrow erythropoietic activity, 2) blood hemoglobin concentration, 3) blood oxygen content, 4) body iron stores, and 5) presence of systemic inflammation. Intestinal iron absorption increases with increased erythropoietic activity, anemia, hypoxemia and decreased iron stores. Conversely, intestinal iron absorption decreases in the presence of inflammation, a process that contributes to the anemia of chronic disease. One of the most important points of regulation is the release of iron from the enterocytes into the systemic circulation by the iron exporter ferroportin: hepcidin seems to play a key role in downregulating this process as well as similarly dowregulating the release of iron from macrophages, thus higher plasma hepcidin levels decreases intestinal iron absorption and iron release from macrophages leading to low plasma iron levels, thus restricting bone marrow erythropoitic activity and vice versa. However, it is also believed that anti-inflammatory cytokines such as IL-6 induces production of hepcidin causing a diversion of iron traffic leading to iron retention in macrophages and an iron–restricted erythropoiesis. The proposed role for hepcidin in normal iron homeostasis is shown in the following figure:
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Figure 1. Hepcidin synthesis in the liver and its effects on iron metabolism. Hepatic
sinusoids (S, pink) are lined by endothelial cells (green) and Kupffer cells (K,green). Exposure of these cells to microbes or highly iron-saturated transferrin (Fe/Tf) causes the release of IL-6 and possibly other signals (red arrows) that act on hepatocytes (H, light blue cells) to induce the synthesis and secretion of hepcidin (yellow arrows). Plasma hepcidin (large yellow arrows) inhibits iron uptake in the duodenum and iron release from macrophages in the spleen and elsewhere (Tomas Ganz, Blood, 102: 783-788, 2003).
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| Hepcidin assay |
| Serum and urine hepcidin can be measured using a newly developed surface-enhanced laser-desorption /ionization time-of-flight mass spectrometry method (SELDI-TOF MS method) (Kemna et al. Blood 2005). Recently, the hepcidin assay was further optimized by the use of hepcidin derivates as internal standards to control for matrix effects and allowing value assess-ment (Kemna et al. 2007). In humans, hepcidin levels displays a clear circadian rhythm, similar to serum iron levels, that was more pronounced for serum than for urine.
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| Conclusion: |
| The recent discovery of hepcidin as an iron regulatory hormone secreted by the liver and having a central role in iron homeostasis suggests that the liver plays a central role in determining how much iron is absorbed from the intestine, and how much iron is distributed between sites of utilization and storage. This discovery could pave the way for novel diagnostic strategies of iron disorders and monitoring their treatment. Hepcidin might also be used to monitor the course of anemia and its improvement. Plasma hepcidin level as a new laboratory test could therefore be a better substitute for serum iron in coming years. With the availability of hepcidin assay it is also hoped to improve the specificity of the diagnosis of functional versus true iron deficiency in anemia of chronic disease and related conditions.
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| References: |
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| المجلد 4 ,
العدد 8
, ذو الحجة 1428 - كانون الثاني (يناير) 2008 |
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