Circulating Human Hepcidin-25 Concentrations Display a Diurnal Rhythm, Increase with Prolonged Fasting, and Are Reduced by Growth Hormone Administration

• Published in: Clinical chemistry (Baltimore, Md.) Vol. 58; no. 8; pp. 1225 - 1232
• Main Authors: TROUTT, Jason S, RUDLING, Mats, PERSSON, Lena, STAHLE, Lars, ANGELIN, Bo, BUTTERFIELD, Anthony M, SCHADE, Andrew E, GUOQING CAO, KONRAD, Robert J
• Format: Journal Article
• Language: English
• Published: Washington, DC American Association for Clinical Chemistry 01.08.2012; Oxford University Press
• Subjects: Adult; Aged; Amino acids; Analytical, structural and metabolic biochemistry; Antimicrobial Cationic Peptides - blood; Biological and medical sciences; Birds; Chronic illnesses; Circadian Rhythm; Diurnal variations; Enzyme-Linked Immunosorbent Assay; Erythropoiesis; Fasting; Fundamental and applied biological sciences. Psychology; Hepcidins; Human Growth Hormone - therapeutic use; Humans; Immunoassay; Investigative techniques, diagnostic techniques (general aspects); Iron; Medical sciences; Medicin och hälsovetenskap; Middle Aged; Molecular biophysics; Reference Values; Rodents; Sensitivity and Specificity; Sleep; Sleep Deprivation; Studies; Time Factors; Young Adult; Human; Fasting; Rhythm; Increase; Biochemistry; Concentration; Somatotropin; Reduction; Adenohypophyseal hormone; Clinical biology; Molecular biology; Fast; Hepcidin; Prolonged
• ISSN: 0009-9147; 1530-8561; 1530-8561
• DOI: 10.1373/clinchem.2012.186866

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. 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. 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. 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.