Circulating human hepcidin-25 concentrations display a diurnal rhythm, increase with prolonged fasting, and are reduced by growth hormone administration.
BACKGROUND
Hepcidin-25 reduces iron absorption by binding to the intestinal iron transporter ferroportin and causing its degradation. Currently, little is known about the basal regulation of circulating hepcidin-25. In addition, although erythropoietin administration has been reported to decrease the circulating hepcidin concentration, information is limited regarding how other stimulators of erythropoiesis, such as growth hormone (GH), might alter hepcidin-25 concentrations.


METHODS
We used a sensitive and specific hepcidin-25 dual-monoclonal antibody sandwich immunoassay to measure hepcidin-25 in healthy human volunteers at various time points throughout the day and during 3 days of fasting and subsequent refeeding. We also measured hepcidin-25 concentrations in healthy volunteers after GH administration.


RESULTS
In healthy individuals, hepcidin-25 concentrations displayed a diurnal variation, with concentrations being lowest in the early morning and steadily increasing throughout the day before declining during the evening hours, a pattern that was not influenced by food intake. Prolonged fasting produced statistically significant increases in hepcidin-25 concentrations. Refeeding reversed this process, and GH administration markedly decreased hepcidin-25 concentrations.


CONCLUSIONS
Our results indicate that in humans, hepcidin-25 exhibits diurnal changes that can be altered by prolonged fasting, which increases hepcidin-25 concentrations approximately 3-fold after 3 days of fasting, possibly owing to a suppression of erythropoiesis that may occur during the fasting state to preserve tissue iron concentrations. In contrast, GH administration decreased hepcidin-25 concentrations by approximately 65%, presumably by stimulating erythropoiesis. These results indicate that circulating hepcidin-25 concentrations display much more dynamic and rapid variation than might have been anticipated previously.
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
Jason S
JS
Troutt
Mats
M
Rudling
Lena
L
Persson
Lars
L
Ståhle
Bo
B
Angelin
Anthony M
AM
Butterfield
Andrew E
AE
Schade
Guoqing
G
Cao
Robert J
RJ
Konrad
D000328:Adult; D000368:Aged; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D002940:Circadian Rhythm; D004797:Enzyme-Linked Immunosorbent Assay; D004920:Erythropoiesis; D005215:Fasting; D064451:Hepcidins; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D012016:Reference Values; D012680:Sensitivity and Specificity; D012892:Sleep Deprivation; D013997:Time Factors; D055815:Young Adult
D023181:Antimicrobial Cationic Peptides; D064451:Hepcidins; C545475:hepcidin 25, human; D019382:Human Growth Hormone