Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans

Mikael Lehtihet, Ylva Bonde, Lena Beckman, Katarina Berinder, Charlotte Hoybye, Mats Rudling, John H Sloan, Robert J Konrad, Bo Angelin, Mikael Lehtihet, Ylva Bonde, Lena Beckman, Katarina Berinder, Charlotte Hoybye, Mats Rudling, John H Sloan, Robert J Konrad, Bo Angelin

Abstract

Objective: Hepcidin reduces iron absorption by binding to the intestinal iron transporter ferroportin, thereby causing its degradation. Although short-term administration of testosterone or growth hormone (GH) has been reported to decrease circulating hepcidin levels, little is known about how hepcidin is influenced in human endocrine conditions associated with anemia.

Research design and methods: We used a sensitive and specific dual-monoclonal antibody sandwich immunoassay to measure hepcidin-25 in patients (a) during initiation of in vitro fertilization when endogenous estrogens were elevated vs. suppressed, (b) with GH deficiency before and after 12 months substitution treatment, (c) with hyperthyroidism before and after normalization, and (d) with hyperprolactinemia before and after six months of treatment with a dopamine agonist.

Results: In response to a marked stimulation of endogenous estrogen production, median hepcidin levels decreased from 4.85 to 1.43 ng/mL (p < 0.01). Hyperthyroidism, hyperprolactinemia, or GH substitution to GH-deficient patients did not influence serum hepcidin-25 levels.

Conclusions: In humans, gonadotropin-stimulated endogenous estrogen markedly decreases circulating hepcidin-25 levels. No clear and stable correlation between iron biomarkers and hepcidin-25 was seen before or after treatment of hyperthyroidism, hyperprolactinemia or growth hormone deficiency.

Conflict of interest statement

Competing Interests: JHS and RJK are employed by Ely Lilly & Co. This does not alter the authors adherence to PLOS ONE policies on sharing data and materials.

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