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Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element
Hou, Yanli; Zhang, Shuping; Wang, Lei; Li, Junping; Qu, Guangbo; He, Jiuyang; Rong, Haiqin; Ji, Hong; Liu, Sijin
2012
Source PublicationGenetics & Heredity
ISSN0378-1119
Volume511Issue:2Pages:398-403
AbstractIron 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. (C) 2012 Elsevier B.V. All rights reserved.
Department环境化学与生态毒理学国家重点实验室
KeywordEstrogen Hepcidin Iron Ovariectomy Estrogen Response Element
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Document Type期刊论文
Identifierhttps://ir.rcees.ac.cn/handle/311016/8051
Collection环境化学与生态毒理学国家重点实验室
Recommended Citation
GB/T 7714
Hou, Yanli,Zhang, Shuping,Wang, Lei,et al. Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element[J]. Genetics & Heredity,2012,511(2):398-403.
APA Hou, Yanli.,Zhang, Shuping.,Wang, Lei.,Li, Junping.,Qu, Guangbo.,...&Liu, Sijin.(2012).Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element.Genetics & Heredity,511(2),398-403.
MLA Hou, Yanli,et al."Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element".Genetics & Heredity 511.2(2012):398-403.
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