Serum hepcidin: reference ranges and biochemical correlates in the general population

Galesloot, Tessel E.; Vermeulen, Sita H.; Geurts-Moespot, Anneke; Klaver, Siem M.; Kroot, Joyce J.C.; Tienoven, Dorlene van; Wetzels, Jack F.M.; Kiemeney, Lambertus A.; Sweep, Fred C.G.J.; Heijer, Martin den; Swinkels, Dorine W.

doi:10.1182/blood-2011-02-337907

Cited by 267 publications

(306 citation statements)

References 42 publications

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“…Meanwhile, hepatic hepcidin expression was also enforced in OVX mice, relative to SHAM mice, indicating restrained iron absorption and iron egress in response to hepcidin-induced FPN degradation. In parallel to the findings from the current animal study, recent clinical investigations also identified increased serum hepcidin concentrations in postmenopausal women, relative to premenopausal women [64,65]. To this end, the induction of FPN was compensated by the increase of hepcidin in the absence of estrogen in mice.…”

Section: Discussionsupporting

confidence: 83%

Estrogen contributes to regulating iron metabolism through governing ferroportin signaling via an estrogen response element

Qian

Yin

Chen

et al. 2015

Cellular Signalling

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Ferroportin (FPN) is the only known iron exporter in mammalian cells, and is universally expressed in most types of cells. FPN signaling plays a crucial role in maintaining iron homeostasis through governing the level of intracellular iron. Serum iron storage is conversely related with the estrogen level in the female bodies, and women in post-menopause are possibly subjected to iron retention. However, the potential effects of estrogen on iron metabolism are not clearly understood. Here, FPN mRNA transcription in all selected estrogen receptor positive (ER+) cells was significantly reduced upon 17β-estradiol (E2) treatment; and this inhibitory effect could be attenuated by ER antagonist tamoxifen. Likewise, in murine bone marrow-derived macrophages (BMDMs), FPN reduction with elevated intracellular iron (reflected by increased ferritin) was observed in response to E2; however, ferritin level barely responded to E2 in FPN-null BMDMs. The observation of inhibition of FPN mRNA expression was not replicated in ER − cells upon E2. A functional estrogen response element (ERE) was identified within the promoter of FPN, and this ERE was responsible for the suppressive effect of E2 on FPN expression. Moreover, ovariectomized (OVX) and sham-operated (SHAM) mice were used to further confirm the in vitro finding. The expression of hepatic FPN was induced in OVX mice, compared to that in the SHAM mice. Taken together, our results demonstrated that estrogen is involved in regulating FPN expression through a functional ERE on its promoter, providing additional insights into a vital role of estrogen in iron metabolism.

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Section: Discussionsupporting

confidence: 83%

Estrogen contributes to regulating iron metabolism through governing ferroportin signaling via an estrogen response element

Qian

Yin

Chen

et al. 2015

Cellular Signalling

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“…The results from the current study are consistent with an epidemiological observation, demonstrating that serum hepcidin is higher in postmenopausal women than premenopausal women (Galesloot et al, 2011). The mechanism underlying the increased hepcidin expression upon estrogen deficiency has not been recognized thus far.…”

Section: Elevated Hepcidin Expression In Liver Devoid Of Endogenous Esupporting

confidence: 91%

Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element

Hou

Zhang

Wang

et al. 2012

Gene

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162

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a b s t r a c t a r t i c l e i n f oIron is essential for the human being, involving in oxygen transport, energy metabolism and DNA synthesis. Iron homeostasis is tightly governed by the hepcidin-ferroportin axis, of which hepcidin is the master regulator. Excess iron is associated with various diseases including osteopenia and osteoporosis, which are closely related to the alternation of the endogenous estrogen level. To verify the biological effect of estrogen on iron metabolism, we established a mouse model of estrogen deficiency by ovariectomy. We demonstrated that the hemoglobin content and serum iron level decreased, whereas the tissue iron level in liver and spleen increased in the ovariectomized mice. Moreover, the transcription of hepatic hepcidin was elevated in ovariectomized mice compared to the control mice. We further demonstrated that there was an estrogen response element (ERE) in the promoter region of the hepcidin gene. The assay using the luciferase reporter system confirmed the existence of a functional ERE in the hepcidin promoter, as the estradiol treatment reduced hepcidin expression in cells transfected with ERE-intact construct, with no response to estradiol in cells transfected with ERE-devoid construct. In conclusion, estrogen greatly contributes to iron homeostasis by regulating hepatic hepcidin expression directly through a functional ERE in the promoter region of hepcidin gene. These findings might help build a better understanding towards the etiology of postmenopausal osteoporosis accompanied by excess tissue iron (such as iron retention of osteoclasts in bone) under estrogen deficiency.

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“…However, the additive value of hepcidin over ferritin in the diagnosis of ID is yet questionable, since ferritin was the most important predictor of hepcidin at all times of measures. This is similar to results reported in previous studies in both children and adults (8,12). Furthermore, differences in ferritin between infants with and those without ID at the age of 4 mo were present already at the age of 1 wk, whereas no differences were observed in hepcidin concentrations at that age.…”

Section: Articlessupporting

confidence: 81%

Serum hepcidin in infants born after 32 to 37 wk of gestational age

et al. 2015

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Background: Preterm infants are at risk of iron deficiency (ID). Hepcidin has been suggested as a good additional indicator of ID in preterm infants, next to ferritin. Methods: In a prospective observational study, we analyzed serum hepcidin in 111 infants born after 32+0 to 36+6 wk gestational age during the first 4 mo of life. results: Hepcidin concentrations decreased during the first 4 mo of life, and concentrations were lower in infants with ID compared to those without ID. Infants who developed ID at the age of 4 mo had already significantly lower levels of hepcidin at 1.5 mo of age, while ferritin was already significantly lower at the age of 1 wk. conclusion: Hepcidin concentrations of late preterm infants decrease during the first 4 mo of life. This decrease, which parallels a decrease of ferritin concentration, we interpret as a physiological response, aiming to increase iron availability. Hepcidin concentrations are lower in infants with ID compared with those without ID, with a notable change already observed at 1.5 mo of age. Hepcidin can be used as an early marker of ID, although an additive value of hepcidin over ferritin in the diagnosis of ID is not present.

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Serum hepcidin: reference ranges and biochemical correlates in the general population

Cited by 267 publications

References 42 publications

Estrogen contributes to regulating iron metabolism through governing ferroportin signaling via an estrogen response element

Estrogen contributes to regulating iron metabolism through governing ferroportin signaling via an estrogen response element

Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element

Serum hepcidin in infants born after 32 to 37 wk of gestational age

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