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PubMed1991

Demonstration of an interaction between transferrin and lipopolysaccharide--an in vitro study.

Transferrin is reported to be a major lipopolysaccharide binding protein of human plasma, at least in vitro. By use of the limulus-amebocyte-lysate test the influence of transferrin on endotoxicity was studied. In the absence of any other protein human iron-free transferrin was able to strongly enhance endotoxicity in a concentration-dependent manner. Similar results were obtained when transferrin was added to primarily heat-inactivated plasma. Even in this assay the endotoxin recovery increased when transferrin was exogenously added. On the other hand, transferrin inhibited endotoxicity when inactivation of the plasma samples was performed after the addition of endotoxin and transferrin. These results lead to the conclusion that transferrin in fact interacts with lipopolysaccharide in a biologically important manner. In order to achieve neutralization of endotoxin, however, other plasma constituents are needed. The hypothetical function of transferrin is possibly a disaggregation of lipopolysaccharide micelles, following the interaction between the two molecules. The present data should justify further studies in order to clarify a possible benefit of the substitution of transferrin during gram-negative sepsis.

Blood Physiological Phenomena↗
PubMed2005

Separation of beta2-transferrin by denaturing gel electrophoresis to detect cerebrospinal fluid in ear and nasal fluids.

BACKGROUND: Cerebrospinal fluid (CSF) leakage is a critical condition with a substantial risk of meningitis. We investigated the use of transferrin isoform analysis as a diagnostic marker for detection of CSF leakage in fluid samples. METHODS: We analyzed 241 samples from patients with CSF leakage, most commonly presenting as otorrhea or rhinorrhea, by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with subsequent Western blotting and immunostaining for transferrin. Tears, saliva, nasal fluid, and ear secretions (20 samples each) were analyzed in parallel, and normal human serum served as a control in each experiment. We compared the minimum volume of added CSF that could be detected in secretions by our assay with the minimum volume detected by the prostaglandin-D synthase (beta-trace) test. CSF was admixed with blood in different proportions to determine the influence of blood contamination on the transferrin pattern. RESULTS: In all CSF samples, beta1- and beta2-transferrin were present in nearly equal amounts. In tears and ear secretions, beta2-transferrin migrated in the gel in the same manner as in CSF, but its concentration was noticeably lower than that of beta1-transferrin, a difference that allowed a clear distinction from the transferrin pattern of CSF. In saliva, both transferrin isoforms were also present but could be distinguished from those of other fluids by electrophoretic migration pattern rather than relative concentrations. With the beta-trace test, a minimum of 5 microL of CSF was needed for detection, whereas our beta2-transferrin assay yielded a signal of comparable intensity with a minimum of 2 microL of CSF. CONCLUSION: Analysis of the transferrin microheterogeneity pattern by SDS-PAGE for the identification of CSF leakage is a highly sensitive and specific method that merits consideration as a routine technique.

Biomarkers↗
PubMed1993

Transferrin gene expression in the mammary gland of the rat. The enhancing effect of 17 beta-oestradiol on the level of RNA is tissue-specific.

We have investigated the physiological factors which regulate transferrin gene expression in the mammary gland of the rat. Our studies by dot blot analysis have demonstrated that multiple doses of 17 beta-oestradiol (OE2; 0.5 mg/kg per day for 3 days) elicit a specific 3.5-fold increase in the transferrin mRNA levels in the mammary glands of virgin rats. The hormonal action of OE2 in mammary tissue was specific for the transferrin gene, as judged by hybridization with beta-actin cDNA. The accumulation of transferrin mRNA induced by OE2 treatment was similar to the developmentally regulated expression of the gene observed during the reproductive cycle. The steady-state level of mammary transferrin mRNA increased by up to 4.5-fold at day 21 of lactation, when compared with virgin and pregnant rats. Our results show that the pattern of transferrin gene expression is different in mouse and rat mammary glands. The specific response of the transferrin gene to OE2 was not found in the liver or in the uterus. In the uterus alone, OE2 produced a significant increase in the content of nucleic acids and also induced the accumulation of transferrin and beta-actin mRNAs. We have detected for the first time an induction of transferrin gene expression in the mammary gland in response to OE2, and these results support the view that the pattern of transferrin gene multi-modulated expression is tissue- and species-specific.

Animals↗
PubMed1999

[Clinical importance of determining levels of circulating transferrin receptors in blood].

Circulating serum transferrin receptor level was measured using mouse monoclonal antibody against transferrin receptor (Orion Diagnostica, Finland) in 126 patients with various disorders of erythropoiesis and the results were compared to those obtained form control group consisted of 30 healthy volunteers with normal iron stores. Serum transferrin receptor level was significantly elevated in patients with iron deficiency and in all patients with hyperplastic erythropoiesis (hereditary spherocytosis, immune hemolytic anemia, beta thalassemia, myelodysplasia). Measurement of circulating serum transferrin receptor level was a sensitive indicator of iron depletion as well as a helpful parameter in differential diagnosis between iron deficiency and anemia of chronic disease where circulating transferrin receptor level was not elevated. Index transferrin receptor/ferritin calculated as a ratio of circulating serum transferrin receptor level to log serum ferritin level was a more sensitive parameter than measurement of serum transferrin receptor not only for determination of patients with anemia of chronic disease, but also for discrimination of patients with elevated serum transferrin receptor level due to true iron deficiency from those with high serum transferrin receptor level caused by relative iron deficiency in hyperplastic erythropoiesis.

Diagnosis, Differential↗
PubMed2001

Reference centiles for serum ferritin and percentage of transferrin saturation, with application to mutations of the HFE gene.

BACKGROUND: The gene that causes most cases of hereditary hemochromatosis is designated HFE. Individuals with mutations in the HFE gene may have increased serum iron, transferrin saturation, and ferritin concentrations relative to individuals with the wild-type genotype. METHODS: We generated reference centiles for percentage of transferrin saturation and serum ferritin concentrations in normal (wild-type), healthy Caucasian adults. We then examined transferrin and ferritin concentrations relative to these centiles in 81 individuals homozygous for the major hemochromatosis mutation C282Y and 438 individuals with the compound heterozygous HFE genotype C282Y/H63D. RESULTS: Serum ferritin concentrations, but not percentage of transferrin saturation, in normal, healthy women tended to increase sharply as they progressed through menopause. Transferrin and serum ferritin centiles for normal, healthy females were lower than the corresponding centiles in normal, healthy males. C282Y homozygotes had abnormally high transferrin saturation and serum ferritin values relative to the wild types. Compound heterozygotes appeared to be a mixture of individuals with unexceptional transferrin and ferritin values and those with abnormally large values similar to the homozygotes, with equal proportions of each. CONCLUSIONS: There are age- and sex-related differences in reference centiles for the percentage of transferrin saturation and serum ferritin concentrations in normal, healthy adults. Individuals homozygous for the C282Y mutation in the HFE gene have abnormal transferrin saturation and serum ferritin values relative to the reference population; penetrance with the compound heterozygotes, as reflected by abnormal transferrin and ferritin values, is less than with the homozygotes.

Adult↗
PubMed2002

Correlation between serum transferrin level and prognosis in patients receiving total parenteral nutrition.

BACKGROUND: Transferrin is a useful index of visceral protein, but it is unknown whether changes in the level of transferrin can be used as a prognostic marker for patients receiving nutrition support. METHODS: Consecutive in one-year period, we recorded the data of 325 patients who with unusable gastrointestinal tract received total parenteral nutrition (TPN) for more than 2 weeks. The data included the levels of serum transferrin, albumin, total bilirubin, hemoglobin and white blood cell before and after 2-week nutrition support. Age, sex, body weight, diagnosis, and hospital outcome were also recorded. A total of 305 patients with complete initial data and 221 patients with data on TPN-induced level change were enrolled and evaluated statistically. RESULTS: The mortality rate was 47.6% in the group of patients who showed no increase of serum transferrin after 2 weeks of TPN. Univariate analysis revealed that the initial level and TPN-induced changes of serum transferrin, albumin and total bilirubin were significantly correlated with patient survival. However, multivariate analysis showed that the initial level of transferrin, albumin, total bilirubin and the TPN-induced level changes in transferrin were independent factors significantly correlated with patient survival. Two of the most the significant factors among them were initial level of transferrin (p < 0.0001, odds ratio = 2.4838) and change in serum transferrin level after 2 weeks of TPN (p < 0.0001, odds ratio = 2.664). CONCLUSIONS: Changes in serum transferrin level in patients with intestinal failure who received TPN for 2 weeks appear to be a good indicator of patient outcome.

Adult↗
PubMed1991

The distribution of cerebral expression of the transferrin gene is species specific.

Various plasma proteins, for example, transferrin, are synthesized not only in the liver, but also in the brain. The proportion of transferrin mRNA in total RNA from different regions of brains from various mammalian species was studied by Northern blot analysis. Absolute amounts of transferrin mRNA were determined in brain, choroid plexus, and liver from rats, sheep, and pigs by hybridization in solution followed by ribonuclease protection assay. Corrections for differences in yields of RNA were made using internal RNA standards. Large proportions of transferrin mRNA in total RNA and high absolute levels of transferrin mRNA in choroid plexus were found only in rats. Small proportions of transferrin mRNA were observed in RNA from choroid plexus from mice, dogs, and rabbits, while no transferrin mRNA at all was detected in choroid plexus from humans, sheep, pigs, cows, and guinea pigs. In further analysis of sheep and pigs, various amounts of transferrin mRNA were found in many parts of the brain, in contrast to the absence of transferrin mRNA from choroid plexus. In conclusion, a striking species specificity was observed for the pattern of cerebral expression of the transferrin gene.

Amino Acid Sequence↗
PubMedDate not supplied

Transferrin receptor expression in the human placenta.

Iron transport from the mother to the fetus is mediated by transferrin receptors located at the maternofetal interface of the placenta. Transferrin receptors bind iron-loaded transferrin molecules from the maternal plasma, thus allowing iron uptake by trophoblastic cells which then deliver the metal to the fetal plasma. We have measured the transferrin receptor content in the placentas from 16 normal-term pregnancies and investigated the relationships between transferrin receptor expression and non-haem iron content, as well as maternal and fetal iron status. Transferrin receptor content was evaluated indirectly by determining the transferrin binding capacity of a placenta extract. Transferrin receptor content of the placenta ranged from 20 to 154 micrograms/g of tissue, with a mean value of 96 +/- 37 micrograms/g. The mean non-haem iron content was 78 +/- 11 micrograms/g of tissue, corresponding to 47 +/- 10 mg for the whole placentas. The amount of transferrin receptors in the placenta was found to be inversely related to the amount of non-haem iron (r = 0.64; p less than 0.025). No significant relationship was observed between each of these two parameters and the iron status of either the mother or the fetus. We conclude that placental non-haem iron, which represents a storage form of this element, is likely to play a regulatory role in the expression of transferrin receptors, and consequently in the process of iron uptake by the placenta.

Female↗
PubMed1989

[Anemia in malignant tumor diseases. II. Tumor-induced loss of transferrin as a cause of the development of anemia based on a rat model].

The cellular uptake and lysosomal accumulation of 67Ga-labelled transferrin within tumors of different malignancy were examined using tissue fractionation and immunological techniques. As tumor models the slowly growing Morris hepatoma 5123 C, the moderately growing Novikoff hepatoma and the fast and aggressive Yoshida hepatoma AH130 were investigated. Isolation of subcellular fractions of tumor homogenates was performed by differential centrifugation and density-gradient centrifugation. The intracellular 67Ga-transferrin was found to be highly concentrated within the purified lysosomes. The transferrin within the lysosomal fraction was identified by radial immunodiffusion technique using monospecific antiserum. The accumulation of 67Ga-transferrin by the tumors resulted in a faster disappearance of 67Ga-transferrin from the blood. This loss of circulating 67Ga-transferrin correlated with the proliferation activity and the spread of the tumors. Since transferrin is indispensible for the utilization of iron by the heme-synthesizing red cell precursors, transferrin concentration in the blood is the limiting factor for the utilization of iron in hemoglobin synthesis. Thus, in a further series of experiments we investigated the development of anemia in tumor-bearing rats. With increasing tumor mass a progressive fall of hemoglobin concentration was found. The anemia was more severe in the faster growing Novikoff hepatoma than in the slowly growing Morris hepatoma. The most significant reduction of hemoglobin concentration was found in the very fast growing Yoshida hepatoma. After total tumor resection hemoglobin concentration and red blood cell count normalized completely within 6-8 weeks. We conclude from these data that the uptake of transferrin by the tumor cells results in a faster disappearance of transferrin from the blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗
PubMed1988

Human T lymphotropic virus I infection deregulates surface expression of the transferrin receptor.

Human T-lymphotropic virus I (HTLV-I) is an etiologic agent in adult T cell leukemia. In an effort to understand the relationship between HTLV-I infection and malignant transformation, we have examined transferrin receptor expression in HTLV-I-infected cells. Transferrin receptor expression in normal T cells is tightly regulated and essential for cell proliferation. We have used matched T cell sets originating from a normal donor, consisting of tetanus toxoid-specific normal T cell clones (TM3 and TM5) and their in vitro HTLV-I-infected counterparts (TM3H and TM5H). Using these matched sets of virus-infected and normal T cells, we have determined that HTLV-I infection leads to hyperexpression of surface transferrin receptors (five- to six-fold higher than normal counterparts). Although the growth rates of the virus-infected cells did not differ significantly from their normal controls, HTLV-I-infected cells constitutively hyperexpressed surface transferrin receptors, whereas the level of surface receptor expression of normal counterpart cells varied during the cycle of antigenic stimulation. Immunoprecipitation of total (surface plus cytoplasmic) transferrin expression showed that the HTLV-I-infected cells did not possess a greater total number of transferrin receptors than their normal counterparts. This data was supported by Northern blot analysis, which showed equivalent transferrin receptor mRNA expression in HTLV-I-infected and uninfected cells. Functional analysis revealed a marked defect in 59Fe-transferrin internalization in the HTLV-I-infected cells. Furthermore, the HTLV-I-infected cells showed markedly decreased transferrin receptor phosphorylation and internalization in response to active phorbol ester. Thus the data demonstrate that in peripheral blood T cells, HTLV-I infection is accompanied by surface transferrin receptor overexpression secondary to subcellular redistribution and defective internalization.

Cell Membrane↗
PubMed1985

Regulation of heme synthesis in erythroid cells: hemin inhibits transferrin iron utilization but not protoporphyrin synthesis.

The inhibition of delta-aminolevulinic acid (ALA) synthase activity by heme is commonly thought to regulate the overall rate of heme synthesis in erythroid cells. However, since heme inhibits erythroid cell uptake of iron from transferrin, we have tested the hypothesis that in reticulocytes heme regulates its own synthesis by controlling the cellular acquisition of iron from transferrin rather than by controlling the synthesis of ALA. We found that hemin added to reticulocytes in vitro inhibits not only the total cell incorporation of 59Fe from transferrin but also the incorporation of [2-14C]-glycine and transferrin-bound 59Fe into heme. However, hemin did not inhibit [2-14C]-glycine incorporation into protoporphyrin. Furthermore, cycloheximide, which increases the level of non-hemoglobin heme in reticulocytes, also inhibited [2-14C]-glycine into heme but not into protoporphyrin. With high concentrations of ferric pyridoxal benzoylhydrazone (Fe-PBH), which, independent of transferrin and transferrin receptors, can be used as a source of iron for heme synthesis in reticulocytes, significantly more iron is incorporated into heme than from saturating concentrations of Fe-transferrin. This suggests that some step (or steps) in the pathway of iron from extracellular transferrin to protoporphyrin limits the overall rate of heme synthesis in reticulocytes. In addition, hemin in concentrations that inhibit the utilization of transferrin-bound iron for heme synthesis has no effect on the incorporation of iron from Fe-PBH into heme. Our results indicate that in reticulocytes heme inhibits and controls the utilization of iron from transferrin but has no effect on the enzymes of porphyrin biosynthesis and ferrochelatase. This mode of regulation of heme synthesis may be a specific characteristic of the hemoglobin biosynthetic pathway.

2,2'-Dipyridyl↗
PubMed1979

A transferrin-mediated uptake of gallium-67 by EMT-6 sarcoma. I. Studies in tissue culture.

We have studied the in vitro uptake of gallium-67 by exponentially growing EMT-6 sarcoma cells in long-term tissue culture. In this system, the addition of transferrin to the medium was required before an appreciable cellular uptake of Ga-67 occurred. The transferrin effect was complex, with an initial stimulation to a peak cell-to-medium ratio of 8--10:1 at low concentrations of transferrin (0.2 mg/ml), followed by a gradual decline in uptake as transferrin in the medium was increased further. EMT-6 tumor-cell uptake of Ga-67 was probably mediated by a specific cellular receptor for transferrin. Scatchard analysis of the EMT-6 cellular binding of human transferrin labeled with iodine-125 indicated a cellular receptor with affinity for transferrin of 5 X 10(6) l/mole and abundance of 500,000 receptors per cell. Over the experimental range of transferrin concentration in the medium, the observed uptake of Ga-67 was closely correlated with the degree of formation of Ga-67-labeled transferrin and the fraction of transferrin bound to the cellular receptor (N = 69, r = 0.86, p less than 0.0001).

Animals↗
PubMed1977

Transferrin uptake by rabbit alveolar macrophages in vitro.

Rabbit alveolar macrophages were shown to bind 125I-human transferrin in vitro. The binding reaction was characterized by three stages: (1) adsorption of transferrin to the cells, followed by (2) rapid uptake of the protein to reach (3) a constant level of cell-bound transferrin. The latter two stages were dependent upon temperature and metabolic energy. Macrophages released 125I-transferrin rapidly when incubated with unlabelled transferrin. Small quantities of 125I-rabbit and 125I-bovine serum albumin, by comparison, were bound to and released by the cells; the attachment of these proteins may be solely the result of adsorption. Transferrin, 80% saturated with iron, was bound to a greater extent than 10 or 50% saturated transferrin; 10% saturated transferrin was bound more readily than the 50% saturated preparation. The findings are consistent with the presence of a transferrin receptor on the cell membrane of the alveolar macrophage and imply that transferrin may interact directly with this cell type in order to remove or donate iron.

Adsorption↗
PubMed1984

The role of the transferrin receptor in human B lymphocyte activation.

Transferrin receptors are expressed on proliferating cells and are required for their growth. Transferrin receptors can be detected after, but not before, mitogenic stimulation of normal peripheral blood T and B cells. T cells demonstrate a functional requirement for transferrin receptors in the activation process. These receptors, in turn, are induced to appear by T cell growth factor (interleukin 2). In the experiments reported here, we examined the regulation of transferrin receptor expression on activated human B cells and whether these receptors are necessary for activation to occur. Activation was assessed by studying both proliferation and immunoglobulin secretion. We determined that transferrin receptor expression on B cells is regulated by a factor contained in supernatants of mitogen-stimulated T cells (probably B cell growth factor). This expression is required for proliferation to occur, because antibody to transferrin receptor (42/6) blocks B cell proliferation. Induction of immunoglobulin secretion, however, although dependent on phytohemagglutinin-treated T cell supernatant, is not dependent on transferrin receptor expression and can occur in mitogen-stimulated cells whose proliferation has been blocked by anti-transferrin receptor antibody. These findings support a model for B cell activation in which mitogen (or antigen) delivers two concurrent but distinct signals to B cells: one, dependent on B cell growth factor and transferrin receptor expression, for proliferation; and a second, dependent on T cell-derived factors and not requiring transferrin receptors, which leads to immunoglobulin secretion.

Antibodies, Monoclonal↗
PubMed1981

Characterization of the transferrin-binding protein in a human trophoblast.

The physical properties and binding characteristics of the solubilized transferrin-binding protein from BeWo cells, a human choriocarcinoma cell line, were investigated. The binding protein was isolated from 125I-labelled membranes by solubilization followed by immunoprecipitation with anti-human transferrin in the presence of saturating human transferrin. Gel filtration on acrylamide agarose (AcA-22) at 21 degrees C in the absence of transferrin indicates that the transferrin-binding protein has a Stokes' radius of 4.6 nm. In the presence of transferrin, the Stokes' radius of the transferrin-binding BeWo protein increases to 6.3 nm. Parallel sucrose density centrifugation studies indicate that the BeWo protein has a sedimentation coefficient of 9.4 S in the absence of transferrin and 10.9 S in the presence of transferrin. Relative molecular mass calculations from sedimentation studies in H2O and D2O, using the method of Sadler et al (1979), indicate a relative molecular mass of 204,000 for the solubilized receptor and 354,000 for the receptor in the presence of transferrin.

Cells, Cultured↗
PubMedDate not supplied

[Transferrin mRNA from the rat liver].

Highly purified transferrin mRNA was isolated from rat liver using indirect immunoprecipitation of polysomes with antibodies to rat transferrin and poly(U)-sepharose chromatography. Isolated transferrin mRNA was apparently homogeneous in sedimentation and electrophoretic experiments. Its sedimentation coefficient is 20S and molecular weight 925 000 (chain length 2800 nucleotides). The purified mRNA programmed the synthesis of electrophoretically homogeneous precursor of transferrin. The cell-free translation of transferrin mRNA was highly sensitive to the inhibition by cap analogues (pm7G) that seems being indicative of the capped structure of its 5' end. Hybridization of transferrin mRNA with [3H]poly(U) revealed the discrete length distribution of poly(A) sequences in mRNA (96, 45 and 26 mononucleotides). The proportion of double-stranded (nuclease SI-resistant) regions in transferrin mRNA is as high as 50-60%. Transferrin cDNA was synthesized via the reverse transcription of transferrin mRNA with oligo(dT) primer. This cDNA hydridized with mRNA template and with total polysomal RNA at C0t1/2 values 1.5 X 10(-3) and 3.6 X 10(0) mol nucleotides X 1(-1) Xs, respectively. Hence, the purified mRNA preparation is 2500-fold enriched with transferrin-coding sequences in comparison to the total polysomal RNA from rat liver.

Animals↗
PubMed1980

Transferrin gene expression. Effects of nutritional iron deficiency.

Nutritional iron deficiency was produced experimentally by raising newly hatched chicks on an iron-deficient diet for several weeks. During this time, hematocrit and hemoglobin values declined, iron stores were depleted, and the circulating level of transferrin increased 2- to 4-fold. The increase in serum transferrin was related to a similar increase in the rate of transferrin synthesis in liver. In addition, the level of transferrin mRNA sequences, as determined by hybridization to a specific cDNA, increased 2- to 3-fold, and more than 80% of the transferrin mRNA was associated with polyribosomes in both control and iron-deficient liver. These results demonstrate that the induction of transferrin synthesis in iron-deficient chicks is regulated directly by an increase in transferrin mRNA. The iron-mediated effects on transferrin also appear to be gene-specific since the rate of synthesis of serum albumin, the major secretory product of liver, was unaffected by any of the experimental conditions. Furthermore, when iron stores were rapidly replenished by the administration of iron-saturated ferritin, both the rate of transferrin synthesis and the level of transferrin mRNA returned to control values with 2 to 3 days.

Animals↗
PubMed1998

Function and regulation of transferrin and ferritin.

Iron represents a paradox for living systems by being essential for a wide variety of metabolic processes (oxygen transport, electron transport, DNA synthesis, etc) but also having the potential to cause deleterious effects. Because of Iron's virtual insolubility and potential toxicity under physiological conditions, specialized molecules for the acquisition, transport, and storage of iron in a soluble, nontoxic form have evolved to meet cellular and organismal iron requirements. Physiologically, the majority of cells in the organism acquire iron from a well-characterized plasma glycoprotein, transferrin. Iron uptake from transferrin is reasonably well understood, and involves the binding of transferrin to the transferrin receptor, internalization of transferrin within an endocytic vesicle by receptor-mediated endocytosis, and the release of iron from the protein by a decrease in endosomal pH. Most of the transferrin-bound iron is used for the synthesis of hemoglobin by developing erythroid cells. Senescent erythrocytes are internalized by the macrophages that liberate hemoglobin iron and release it back to plasma transferrin at a rate that normally matches the rate of iron transport for erythropoiesis. Unfortunately, the mechanisms and controls involved in the release of iron from macrophages have not been defined. After iron release from transferrin within endosomes, iron passes through the endosomal membrane by ill-understood mechanisms and then enters the poorly characterized intracellular labile pool. Iron in the labile pool that exceeds requirement for the synthesis of functional heme and nonheme iron-containing proteins is stored within the iron-storage protein, ferritin. Evidence in vitro indicates that relatively soluble ferrous iron can enter or be released from ferritin. However, we know virtually nothing about the exchange of iron with ferritin in intact cells, and some evidence indicates that the degradation of the ferritin protein may be an important mechanism for the release of iron within the cell. Cellular iron uptake and storage are coordinately regulated through a feedback control mechanism mediated at the post-transcriptional level by cytoplasmic factors know as iron-regulatory proteins 1 and 2. These proteins "sense" levels of iron in the transit pool and, when iron in this pool is scarce, they bind to stem-loop structures known as iron-responsive elements on the 5' untranslated region of the ferritin mRNA and 3' untranslated region of the transferrin mRNA. Such a binding inhibits translation of ferritin mRNA and stabilizes the mRNA for transferrin receptors. The opposite scenario develops when iron in the transit pool is plentiful. This remarkable regulatory mechanism prevents the expansion of a catalytically active intracellular iron pool, while maintaining sufficient concentrations of the metal for metabolic needs.

Ferritins↗