title: 17β-Estradiol inhibits iron hormone hepcidin through an estrogen responsive element half-site.
abstract: Interaction of estrogen with iron at the systemic level is long suspected, but direct evidence linking the two is limited. In the present study, we examined the effects of 17β-estradiol (E2) on hepcidin, a key negative regulator of iron absorption from the liver. We found that transcription of hepcidin was suppressed by E2 treatment in human liver HuH7 and HepG2 cells, and this down-regulation was blocked by E2 antagonist ICI 182780. Chromatin immunoprecipitation, deletion, and EMSA detected a functional estrogen responsive element half-site that is located between -2474 and -2462 upstream from the start of transcription of the hepcidin gene. After cloning the human hepcidin promoter into the pGL3Luc-Reporter vector, luciferase activity was also down-regulated by E2 treatment in HepG2 cells. E2 reduced hepcidin mRNA in wild-type mice as well as in hemochromatosis Fe gene knockout mice. In summary, our data suggest that hepcidin inhibition by E2 is to increase iron uptake, a mechanism to compensate iron loss during menstruation. This mechanism may also contribute to increased iron stores in oral contraceptive users.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, New York, New York 10016, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yang
authors.forename: Jinlong
authors.initials: J
authors.lastname: Jian
authors.forename: Stuart
authors.initials: S
authors.lastname: Katz
authors.forename: Steven B
authors.initials: SB
authors.lastname: Abramson
authors.forename: Xi
authors.initials: X
authors.lastname: Huang
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors / Q000235:genetics*; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D004247:DNA / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D017353:Gene Deletion; D064451:Hepcidins; D006801:Humans; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D020218:Response Elements; D014158:Transcription, Genetic
chemical_list: D023181:Antimicrobial Cationic Peptides; D004967:Estrogens; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D012333:RNA, Messenger; D004958:Estradiol; D004247:DNA; D007501:Iron