Circulating Hepcidin-25 Is Reduced by Endogenous Estrogen in Humans

PLoS One. 2016 Feb 11;11(2):e0148802. doi: 10.1371/journal.pone.0148802. eCollection 2016.

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.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anemia / blood*
  • Anemia / metabolism
  • C-Reactive Protein / biosynthesis
  • C-Reactive Protein / metabolism
  • Dopamine Agonists / chemistry
  • Estrogens / physiology*
  • Female
  • Ferritins / biosynthesis
  • Ferritins / metabolism
  • Fertilization in Vitro
  • Hepcidins / blood*
  • Human Growth Hormone / deficiency
  • Human Growth Hormone / metabolism
  • Humans
  • Hyperprolactinemia / complications
  • Hyperthyroidism / complications
  • Immunoassay
  • Iron / metabolism
  • Male
  • Middle Aged
  • Prolactinoma / blood
  • Transferrin / biosynthesis
  • Transferrin / metabolism
  • Young Adult

Substances

  • Dopamine Agonists
  • Estrogens
  • Hepcidins
  • Transferrin
  • hepcidin 25, human
  • Human Growth Hormone
  • C-Reactive Protein
  • Ferritins
  • Iron

Grants and funding

The authors received no specific funding for this work. Lilly Research Laboratories, Eli Lilly & Co, provided support in the form of salaries for authors JHS and RJK, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ʻauthor contributionsʼ section.